tag:theconversation.com,2011:/ca/topics/vaccine-trials-22988/articlesVaccine trials – The Conversation2021-06-30T15:52:07Ztag:theconversation.com,2011:article/1632212021-06-30T15:52:07Z2021-06-30T15:52:07ZWill COVID-19 vaccination enthusiasm last? Lessons from polio and H1N1<figure><img src="https://images.theconversation.com/files/408260/original/file-20210624-13-vxe6fk.jpg?ixlib=rb-1.1.0&rect=1%2C0%2C909%2C618&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Two public health nurses vaccinate adults at a polio clinic in Southey, Sask. in 1960.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/lac-bac/49587866686/in/photolist-2m3Vqeq-T7XMum-ovDmHk-oerCAi-odc6cv-tkGxDo-owgyyA-2ixUM9J-xrxZmo-xHttWf-xFN125-xnv3jo-od9pYA-x8jPuc-sG6bND-tAzahh-xb5kzq-xsFWuV-odcPp7">(Canadian Nurses Association fonds. Library and Archives Canada)</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><iframe style="width: 100%; height: 175px; border: none; position: relative; z-index: 1;" allowtransparency="" src="https://narrations.ad-auris.com/widget/the-conversation-canada/will-covid-19-vaccination-enthusiasm-last--lessons-from-polio-and-h1n1" width="100%" height="400"></iframe>
<p>Canadian enthusiasm for COVID-19 vaccination is impressive. After repeated lockdowns, long separations from friends and family and economic losses, Canadians are lining up overnight at <a href="https://toronto.ctvnews.ca/hundreds-line-up-as-pop-up-clinics-offer-covid-19-vaccines-to-children-aged-12-and-over-1.5433466">pop-up clinics</a> and <a href="https://www.thestar.com/news/gta/2021/05/03/miss-out-amid-this-mornings-scramble-to-get-a-vaccine-appointment-for-people-18-in-covid-19-hot-spots-you-werent-alone.html">crashing websites</a> with their eagerness to book appointments.</p>
<p><a href="https://ourworldindata.org/covid-vaccinations">Canada is currently a global leader</a> with over <a href="https://health-infobase.canada.ca/covid-19/vaccination-coverage/">75 per cent of the eligible population</a>, as of June 25, having received their first dose.</p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/410911/original/file-20210712-19-geybnm.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/410911/original/file-20210712-19-geybnm.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/410911/original/file-20210712-19-geybnm.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/410911/original/file-20210712-19-geybnm.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/410911/original/file-20210712-19-geybnm.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/410911/original/file-20210712-19-geybnm.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/410911/original/file-20210712-19-geybnm.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption"></span>
<span class="attribution"><a class="source" href="https://theconversation.com/ca/topics/vaccine-confidence-in-canada-107061">Click here for more articles in our series about vaccine confidence.</a></span>
</figcaption>
</figure>
<p>Does this mean we can stop worrying about vaccine uptake? Experience from history suggests not. As historians <a href="https://doi.org/10.1503/cmaj.171238">Heather MacDougall and Laurence Monnais</a> have argued, people do not get the recommended vaccines for a variety of reasons, including apathy. Another reason is misinformation, like the <a href="https://www.historyofvaccines.org/content/articles/do-vaccines-cause-autism">unfounded and discredited claim that the measles, mumps and rubella vaccine can cause autism</a>. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/private-messages-contribute-to-the-spread-of-covid-19-conspiracies-162725">Private messages contribute to the spread of COVID-19 conspiracies</a>
</strong>
</em>
</p>
<hr>
<p>Some <a href="https://doi.org/10.1080/10810730.2017.1312720">are not convinced</a> that the disease in question will impact them or their families. Others are deterred by the difficulty of accessing the vaccine. More than a few are scared of <a href="https://doi.org/10.1016/j.vaccine.2012.05.011">needles</a>. We have seen all of these factors play out in past epidemics.</p>
<p>We examined the response to polio and the H1N1 vaccines in Canada. At the height of the epidemics, Canadians were keen to get vaccinated, but vaccine enthusiasm waned once the crisis had passed.</p>
<h2>The case of polio</h2>
<p>Parents were terrified by polio in the early decades of the 20th century. Usually striking in the otherwise carefree summer months, <a href="https://www.who.int/news-room/fact-sheets/detail/poliomyelitis">polio could leave children paralyzed</a>. In some cases children were confined in <a href="https://longreads.com/2020/05/26/among-the-last-in-an-iron-lung/">iron lungs</a> and in the very worst cases, death. </p>
<p>The first trial of the Salk polio vaccine took place in the United States in 1954, <a href="https://www.thecanadianencyclopedia.ca/en/article/canada-and-the-development-of-the-polio-vaccine">using a vaccine produced in Toronto’s Connaught Laboratories</a>. </p>
<p>The vaccine proved highly effective. Other laboratories were licensed to product the vaccine, but one of them, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1383764/">the Cutter Laboratories, failed to properly de-activate the polio virus</a> and 10 children died from polio. The U.S. <a href="https://www.nytimes.com/1955/05/07/archives/u-s-halts-flow-of-polio-vaccine-pending-a-study-u-s-halts-flow-of.html">halted the vaccination program</a> on May 7, 1955.</p>
<p>In Canada, a trial using the vaccine produced at the Connaught Laboratories continued. Health officials assured Canadians that the Connaught Laboratories product <a href="https://news.google.com/newspapers?nid=QBJtjoHflPwC&dat=19550509&printsec=frontpage&hl=en">was safe and effective</a>. By June 1956, <a href="https://www.jstor.org/stable/41981152">1.8 million Canadian children had been vaccinated</a>. But this did not eradicate polio — there were significant epidemics in the late 1950s and early 1960s. </p>
<figure class="align-center ">
<img alt="A nurse stands next to man in an iron lung" src="https://images.theconversation.com/files/408414/original/file-20210625-28-jwj8ja.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/408414/original/file-20210625-28-jwj8ja.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/408414/original/file-20210625-28-jwj8ja.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/408414/original/file-20210625-28-jwj8ja.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/408414/original/file-20210625-28-jwj8ja.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/408414/original/file-20210625-28-jwj8ja.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/408414/original/file-20210625-28-jwj8ja.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A photo of a man in an iron lung from July 1957.</span>
<span class="attribution"><span class="source">(Library and Archives Canada)</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>The Salk vaccine schedule required three separate doses, making it a challenge to complete the full course of vaccination. </p>
<p>Many adults believed that polio only impacted children and were reluctant to take the vaccine. <a href="https://www.jstor.org/stable/41981576">Only 10 per cent of Canadian adults</a> had received the required three doses of the Salk vaccine by June of 1959, compared to a rate of 90 per cent among school-aged children. </p>
<p>The year 1959 was one of the worst years for polio in Canada, with nearly <a href="https://www.cpha.ca/story-polio">2,000 paralytic cases</a>. In Montréal <a href="https://news.google.com/newspapers?nid=Fr8DH2VBP9sC&dat=19591015&printsec=frontpage&hl=en">there were over 950 cases and 51 fatalities</a>. Across Canada, more young adults died than children between the ages of five and 19, most of the cases occurring among those who had not been vaccinated. </p>
<p>During the 1959 epidemic people swamped the vaccination clinics in Montréal. And three years later, following <a href="https://news.google.com/newspapers?nid=Fr8DH2VBP9sC&dat=19620829&printsec=frontpage&hl=en">an outbreak in Hull, Que.</a>, residents came to the vaccination clinics in droves. </p>
<h2>Introduction of oral vaccine</h2>
<p>The introduction of the oral polio vaccine (Sabin vaccine) in 1961 led to an uptick in polio vaccinations. </p>
<p>In just three months in 1962, over <a href="https://www.jstor.org/stable/pdf/41983496.pdf">four million Canadians</a> received the oral polio vaccine. Many adults who had resisted earlier appeals to get the Salk vaccine <a href="https://news.google.com/newspapers?nid=Fr8DH2VBP9sC&dat=19620521&printsec=frontpage&hl=en">showed up to sip</a> the tasteless Sabin vaccine, often served on a sugar cube. <a href="https://news.ourontario.ca/88728/page/278074?q=polio+OR+vaccine">Newspapers raved</a> that no needles were necessary. And by the 1970s, polio had all but disappeared in Canada. </p>
<p>When the Salk vaccine came out, parents were very keen to have their children vaccinated, but young adults were not convinced that they were at risk and did not get vaccinated. Only after additional epidemics showed that that they too could die or be paralyzed by polio did adults turn up to get vaccinated. The vaccination effort was further aided by tasty Sabin vaccine.</p>
<figure class="align-center ">
<img alt="Group of people waiting for vaccines" src="https://images.theconversation.com/files/408264/original/file-20210624-23-19pt0mr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/408264/original/file-20210624-23-19pt0mr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=471&fit=crop&dpr=1 600w, https://images.theconversation.com/files/408264/original/file-20210624-23-19pt0mr.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=471&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/408264/original/file-20210624-23-19pt0mr.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=471&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/408264/original/file-20210624-23-19pt0mr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=591&fit=crop&dpr=1 754w, https://images.theconversation.com/files/408264/original/file-20210624-23-19pt0mr.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=591&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/408264/original/file-20210624-23-19pt0mr.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=591&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">People lined up to get their H1N1 vaccination in Oct. 2009 in St. Eustache Que. Waiting times of seven hours were common as vaccination centres were overwhelmed by the demand.</span>
<span class="attribution"><span class="source">THE CANADIAN PRESS/Ryan Remiorz</span></span>
</figcaption>
</figure>
<h2>H1N1 vaccination campaign</h2>
<p>In spring of 2009, a novel H1N1 influenza virus began spreading in <a href="https://doi.org/10.1016/S0140-6736(09)61638-X">Mexico</a>. The first cases were reported in <a href="https://www.thecanadianencyclopedia.ca/en/article/h1n1-flu-of-2009-in-canada">Canada</a> that April.</p>
<p>In June, the <a href="https://www.cdc.gov/h1n1flu/who/">World Health Organization</a> declared H1N1 to be a global pandemic. Like the flu of 1918-19, which killed as many as <a href="https://www.cdc.gov/flu/pandemic-resources/1918-pandemic-h1n1.html">50 million people</a> around the world, the 2009 flu had a disproportionate impact on <a href="https://www.thestar.com/life/health_wellness/news_research/2009/10/28/h1n1_is_serious_but_no_need_to_panic.html">younger people</a>. </p>
<p>That fall, vaccination clinics opened across Canada for priority groups. Early polls showed that only <a href="https://www.thestar.com/life/health_wellness/news_research/2009/10/22/h1n1_vaccine_headed_to_a_clinic_near_you.html">one-third of Canadians</a> planned to get the H1N1 vaccine, which was <a href="https://www150.statcan.gc.ca/n1/pub/82-624-x/2015001/article/14218-eng.htm">on par with seasonal flu shot vaccination rates</a>. Less than <a href="https://doi.org/10.1093/infdis/jis283">perfect efficacy rates</a> of the seasonal flu shot did little to inspire the Canadian public to seek out the H1N1 vaccine. </p>
<p>But four days after vaccination clinics opened in Ontario, a previously healthy <a href="https://toronto.ctvnews.ca/boy-killed-by-h1n1-was-my-best-friend-says-dad-1.447725">boy in Toronto died</a>. The tragic news stirred fear among Ontarians, prompting thousands to <a href="https://www.macleans.ca/news/canada/swine-flu-screw-up/">rush to clinics</a>. Many waited in line for hours, while others were turned away.</p>
<p>Vaccines became available to all Ontarians in November 2009, but by then, people’s fears had eased — it seemed that H1N1 <a href="https://doi.org/10.1503/cmaj.100900">was not as lethal as had originally been feared</a>. </p>
<p>Ultimately, <a href="https://www.thecanadianencyclopedia.ca/en/article/h1n1-flu-of-2009-in-canada">between 40 and 45 per cent</a> of the Canadian population was vaccinated against H1N1. </p>
<p>Once again, vaccine enthusiasm was high in the middle of the crisis, but it diminished after the flu appeared to be less dangerous.</p>
<h2>Lessons for COVID-19</h2>
<p>Polio and H1N1 reveal the complexities of vaccine enthusiasm. People rush to get vaccines when they perceive an immediate health risk to themselves or their family members. But without that fear, it is easier to delay or avoid getting vaccinated.</p>
<p>Many Canadians know someone who has gotten sick from COVID-19 and many have lost friends and family members to the disease. It’s no wonder we are eager to get vaccinated. But enthusiasm may wane as case counts fall. </p>
<p>If it proves that we need boosters, but case counts are low, will people make the same effort to get out to the vaccine clinics?</p>
<p>The biggest challenge may be ensuring the continuing uptake of vaccines once the initial crisis has passed. In addition to measures to <a href="https://theconversation.com/how-canadians-can-use-social-media-to-help-debunk-covid-19-misinformation-155653">combat vaccine misinformation</a>, public health authorities need to ensure that vaccines are readily available and convenient to access. </p>
<p><em>Do you have a question about COVID-19 vaccines? Email us at <a href="mailto:ca-vaccination@theconversation.com">ca‑vaccination@theconversation.com</a> and vaccine experts will answer questions in upcoming articles.</em></p><img src="https://counter.theconversation.com/content/163221/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Catherine Carstairs has received funding from SSHRC, AMS Healthcare and the University of Guelph. This research was funded by a grant from the University of Guelph, SSHRC Institutional Explore Grant.</span></em></p><p class="fine-print"><em><span>Curtis Fraser does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>At the height of polio and H1N1, Canadians were keen to get vaccinated, but vaccine enthusiasm waned once the crisis had passed — what does that mean for COVID-19?Catherine Carstairs, Professor, Department of History, University of GuelphCurtis Fraser, Graduate Student, History, University of GuelphLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1605512021-05-07T10:45:55Z2021-05-07T10:45:55ZCuba’s push for coronavirus vaccine sovereignty<p><em>This is a transcript of episode 14 of The Conversation Weekly podcast ‘<a href="https://theconversation.com/cubas-race-to-make-its-own-coronavirus-vaccine-podcast-160324">Cuba’s race for a coronavirus vaccine + making life’s big decisions</a>’. In this episode, how Cuba is pushing ahead with developing its own coronavirus vaccines – and could be nearing “vaccine sovereignty”. And we hear from a researcher about what he learned from asking hundreds of people about the biggest decisions of their lives.</em></p>
<iframe src="https://embed.acast.com/60087127b9687759d637bade/6093b5079c1bd6195844c91c?cover=true" frameborder="0" allow="autoplay" width="100%" height="110"></iframe>
<p><iframe id="tc-infographic-561" class="tc-infographic" height="100" src="https://cdn.theconversation.com/infographics/561/4fbbd099d631750693d02bac632430b71b37cd5f/site/index.html" width="100%" style="border: none" frameborder="0"></iframe></p>
<p><em>NOTE: Transcripts may contain errors. Please check the corresponding audio before quoting in print.</em></p>
<p>Gemma Ware: Hello and welcome to The Conversation Weekly.</p>
<p>Dan Merino: This week, how Cuba is pushing ahead with the development of its own coronavirus vaccines, and could be nearing vaccine sovereignty.</p>
<p>Amilcar Pérez Riverol: They say, “We can do this, we have been doing this for a long time, so at least we should try.” </p>
<p>Gemma: And we hear from a researcher about what he learnt from asking hundreds of people about the biggest decisions of their lives.</p>
<p>Adrian Camilleri: Many people indicated they spent years thinking about the self-development decisions. </p>
<p>Dan: I’m Dan Merino in San Francisco. </p>
<p>Gemma: And I’m Gemma Ware in London. You’re listening to The Conversation Weekly, the world explained by experts.</p>
<p>Dan: COVID-19 first arrived in Cuba in early March 2020, when three tourists from Italy tested positive for the virus.</p>
<p>Gemma: Throughout last year, Cuba was able to limit the spread of the disease across the island. But case numbers have been increasing in 2021. Currently around 1,000 new cases are being recorded every day.</p>
<p>Dan: By the start of May, Cuba had registered <a href="https://www.statista.com/statistics/1104709/coronavirus-deaths-worldwide-per-million-inhabitants/">675 deaths from COVID</a>. That’s a death rate of 60 people per million, which is pretty good compared to 1,751 per million here in the US, or 1,904 per million in the UK.</p>
<p>Gemma: The pandemic has hit Cuba hard in other ways though, and it’s economy shrunk 11% in 2020. As well as the loss of tourism, an important source of foreign currency for the island, other structural issues, including the strengthening of some US sanctions, have <a href="https://theconversation.com/cubas-economic-woes-may-fuel-americas-next-migrant-crisis-158260">caused a severe economic crisis</a>, which has led to food shortages.</p>
<p>Dan: Now, with cases rising, there’s an urgent need to get people vaccinated. But instead of relying on other countries’ vaccines, Cuba has decided to go it alone. </p>
<p>Gemma: Yeah, Cuba has a strong biotechnology and healthcare sector, and it’s been investing public money in a handful of different candidate vaccines for COVID over the past year.</p>
<p>Dan: For this episode, I’ve spoken to three experts, to help explain how Cuba’s race for a coronavirus vaccine is going, and where it fits into the wider picture of global vaccine diplomacy.</p>
<p>Dan: This is a story about a small country, that despite living under a very restrictive US trade embargo, could be on the cusp of making its own vaccine. But it also illustrates a bigger story about who controls access to pharmaceuticals, and how this makes it much harder for people in the global south to get the vaccines and drugs they need.</p>
<p>Dan: A few months into the pandemic in May 2020, the Cuban president, Miguel Díaz-Canel, began pushing for his country to develop its own COVID-19 vaccine. The country’s biotech sector moved quickly into action, and today there are number of vaccines candidates, and a few are almost ready for use. </p>
<p>Amilcar: Cuba is working with five different a vaccine candidate for COVID-19, two of them in phase 3 of clinical trials. We should refer to as vaccine candidate because they don’t have yet the data related to efficacy and also they don’t have, emergency use authorisation or full use authorisations.</p>
<p>Dan: This is Amilcar Pérez Riverol. He’s a postdoctoral researcher at the University of São Paolo State and a former professor of virology at the University of Havana in Cuba. He has been closely watching the progress of the five vaccine candidates. </p>
<p>Amilcar: Soberena 01, 02 and Soberena plus are being developed by the Finlay Institute of Vaccines. </p>
<p>Dan: The Finlay Institute was set up in the late 90s and is part of BioCubaFarma, a state-run holding company that includes more than 30 research institutes and pharmaceutical manufacturers. In the late 1980s, a precursor to the Finlay Institute developed the world’s first vaccine against meningitis B. Today, the institute produces ten vaccines routinely used within Cuba, but also sends hundreds of millions of doses abroad. </p>
<p>It’s the Finlay Institute which is making Cuba’s three Soberena vaccines. The name Soberena is pregnant with meaning. In Spanish, it means sovereign.</p>
<p>Amilcar: And then you have Abdala and Mambisa, which are being developed mainly by the Center of Genetic Engineering and Biotechnology, Havana.</p>
<p>Dan: Public money is being poured into the development of these vaccine candidates, which involve collaborations between a range of different institutions.</p>
<p>Amilcar: Most of them belonging to BioCubaFarma. </p>
<p>Dan: All five of Cuba’s candidate vaccines are what are called subunit vaccines. Subunit vaccines work by directly injecting a small piece of the targeted virus – a subunit – into a persons body. The body then generates an immune response against the subunit. This is different from mRNA vaccines, like Moderna’s and Pfizer’s – as well as adenovirus vaccines, like Johnson & Johnson and Astrazeneca’s, both of which deliver genetic material into the body and then a person’s own cells produce parts of the virus. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/how-are-covid-19-vaccines-made-an-expert-explains-155430">How are COVID-19 vaccines made? An expert explains</a>
</strong>
</em>
</p>
<hr>
<p>Amilcar: Cuba have a great expertise in working with subunit vaccines. Most of the vaccines that are currently being using are based in the whole spike protein. In the case of Cuba vaccine, they use just part of this protein. </p>
<p>Dan: The specific part of the spike protein used in Cuba’s vaccines is called the RBD - or the receptor binding domain. This is the subunit in the subunit vaccines. </p>
<p>Amilcar: So the idea is that you produce the RBD, and then you immunise people with the RBD so these people are able to produce specific antibodies against the RBD and neutralise the virus. </p>
<p>Dan: Two of Cuba’s vaccine candidates have begun stage three clinical trials, and remember that’s the final stage before a drug or intervention is approved by medical regulators. </p>
<p>Amilcar: So they are running these classic phase 3 clinical trials. And for Soberana 02 they have 44,000 people in the trial, and in the case of Abdala they have 48,000 people. But also they are running a study, they call it intervention study with 150,000 people for Soberana 02. And the number is quite similar for Abdala. And they are particularly running this study with healthcare workers. This is, let’s say a non-classical approach. So far we don’t see this for any other candidate for COVID 19. </p>
<p>Dan: Data on the efficacy of Cuba’s vaccine candidates is still limited, but Amilcar says what information there is, is looking pretty good, at least in the academic pre-prints that have been publishd. In late April, Vicente Vérez Bencomo, director general of the Finlay Institute, <a href="https://www.nature.com/articles/d41586-021-01126-4">told the journal Nature</a> that initial trial phases of the Soberena 02 vaccine generated an antibody response in around 80% of the people who got vaccinated. And that climbed to 100% when those people were given a booster dose of the Soberena Plus vaccine. </p>
<p>Amilcar: They are thinking that they will have the data related to efficacy, to the outcome of phase 3 clinical trials sometime around the end of May, June, or even July. </p>
<p>Dan: That’s pretty good, but other places have been giving vaccines to their population for months now. So, why you might be wondering, did Cuba decide to go it alone and produce its own vaccine? Well, according to Amilcar, it’s kind of because they can. </p>
<p>Amilcar: They say, “OK, we can do this, we have been doing this for a long time, so at least we should try.” Then they have mentioned that the country doesn’t have the money to pay for other vaccines. They say that they don’t have the money to enter in this Covax mechanism for World Health Organization. </p>
<p>Dan: Low- and middle-income countries can get vaccines from Covax for free. But Cuba is considered an upper middle-income nation so it would have to pay. </p>
<p>Amilcar: Also it will take time for the Covax facility to fulfil their commitment, you know, for the amount of those doses we need for immunise the whole population. </p>
<p>Dan: So Cuba decided to go it alone. The process hasn’t been all easy though. </p>
<p>Amilcar: I have to say that the embargo have an impact in Cuba biotechnology.</p>
<p>Dan: Though the US trade embargo on Cuba is not as tight as it once was, it’s still very difficult for Cuban organisations to access pharmacological raw materials and medical equipment, especially since Donald Trump’s toughened sanctions during his presidency. </p>
<p>Amilcar: They need, for example, some equipment that they use to conduct the analysis in the lab. And then you have also problem with some of the ingredients, that you need to produce the vaccine. But so far it looks like they will be able to finish the process of evaluation and also to produce the amount of doses that they will require to immunise the whole Cuban population and also to provide or offer doses to countries that eventually will be interested, for example, Venezuela, Bolivia, Mexico and also Argentina. </p>
<p>Dan: Despite these difficulties, two of the Cuban vaccines are in phase 3 trials as of earl May and Cubans have been enthusiastic.</p>
<p>Amilcar: You can see that a lot of people are going to the place where the clinical trials are taking place to be volunteers. The general idea that I get from people that I talk to in Cuba is that they are confident and they want to be vaccinated as soon as possible. </p>
<p>Dan: But Amilcar also acknowledged concerns about these intervention studies – those are the two studies that have given the vaccine candidates to more than 100,000 health care workers each - and that is despite the fact that the phase 3 trials have yet to show efficacy.</p>
<p>Amilcar: This is a bit unusual, because you are immunising thousands of people with the candidate and you don’t know the efficacy yet. So you have some concern in the general population. </p>
<p>Dan: To be clear, the Cuban vaccines have been shown to be safe. The risk is that they just might not prevent COVID-19. </p>
<p>Amilcar: You will use a lot of resources in immunising a lot of people and you don’t know if this will have the benefits. I mean, for these vaccines, you have three doses. So you have to use a lot of resources to complete and to immunise these amount of people and you don’t know if they are protected and this can have an impact in the rate of infection in the country.</p>
<p>Dan: Pushing ahead with such a large number of vaccinations is certainly risky without efficacy results. Amilcar was waiting to see the results of the phase 3 trials showed, to really see how this whole thing would play out. </p>
<p>So that is where Cuba is at with the vaccine from a technical perspective, but perhaps just as interesting are the social dynamics of the pandemic in Cuba. Cuba is a one-party, communist state. Civil liberties and access to information are pretty severely restricted and expressing dissent can be, well, dangerous. In spite of, or perhaps because of this relationship between the government and people of Cuba, the coronavirus response seems to have been quite good. And this both from the perspective of outsiders, as well as those living on the island. </p>
<p>Jennifer: I’m Jennifer Hosek, I’m a full professor in languages, literatures and cultures at Queens University in Ontario, Canada. </p>
<p>Dan: Jennifer’s research on Cuban film and society means that she’s spent a lot of time there over the years. She’s been following the pandemic situation in the country really closely. Cuba has been able to keep death rates extremely low during the pandemic. She thinks one of the reasons for this is simply the country’s approach to healthcare. </p>
<p>Jennifer: The ratio between provider and patient is a very good one. There are neighbourhood clinics, family doctors, and a cradle-to-grave structure that basically aims to have the person be treated by family doctors that really know them and know them holistically. It’s also, of course, free and it focuses on public health and prevention rather than end of pipe. That also makes the healthcare much more affordable. </p>
<p>Dan: The government’s public health communication campaigns have made Cubans confident about their country’s vaccine strategy and health messaging in general. And there’s history here: this confidence has been earned through science-based campaigns to fight diseases including HIV, Ebola, dengue fever and the Zika virus.</p>
<p>Jennifer: Trust in the government in regards to healthcare that has been built up through many, many decades really stands the government in good stead because when it sends out clear, strong directives that are science-based and public health first, and it says, this is what you must do, and then it explains, why you must do it. And it explains it in different ways to different audiences. </p>
<p>Dan: This includes cartoons for children, where angry “red meanie” viruses are blocked by face masks. It also includes a daily news show with the epidemiologist Dr Fransisco Duran, who explains the science behind COVID-19 in accessible language. But to find out more about how Cubans have reacted to this health messaging, and to the politics around mask wearing during the pandemic, Jennifer surveyed residents of Havana online and later in-person while in Cuba in December and January. </p>
<p>Jennifer: I thought, “Wow! I wonder what’s going on in Cuba.” And you know, I have a big network there. So <a href="https://theconversation.com/the-scene-from-cuba-how-its-getting-so-much-right-on-covid-19-155699">I just started a sort of informal WhatsApp interview</a> using a snowball technique, which means that I started with people that I know and then asked them to interview people that they knew. </p>
<p>I think the most impressive or interesting, I guess, take-home message for me was that most people basically said: “It’s my responsibility to wear a mask because it’s, I’m responsible for myself, but I’m also responsible for others.” And I think that, that this kind of, that kind of idea of, like, “I am” in relation to the other, allows people to think, “I can only be healthy if the other is healthy.” Imagine if the global community thought this way. </p>
<p>Dan: According to Jennifer, the fact that Cuba is trialling five COVID vaccine candidates is because of the state’s dedication to science and the way it has prioritised its citizens’ health. </p>
<p>Jennifer: Cuba invested in healthcare. It invested in healthcare in a big way. They started in the 80s and 90s to build on this medical knowledge and build up biotech and medical research, because the Soviet Union was starting to end and Cuba needed to really stand on its own. And so they developed in this direction building on what they already had.</p>
<p>Dan: Cuba is famous for its medical diplomacy. It sees it as part of its international solidarity effort. Fidel Castro was the first to send Cuban medics to Algeria in 1963 and the country has sent more than 400,000 healthcare professionals to work in 164 countries, most notably this is done through its Henry Reeve Brigades, named after an American who fought, and died, for the Cuban independence forces in the mid-19th century. In late March 2020, Cuba sent 52 groups of doctors and nurses to Italy to help at the peak of the country’s first wave of coronavirus. </p>
<p>Cuba’s track record on healthcare diplomacy also means it’s been able to turn to a network of international collaborators when it’s come to trialling their vaccine candidates. </p>
<p>Jennifer: Cuba is characterised by internationalism and international collaboration and it’s drawing on this. China is one of the partners. Iran is another partner with which it’s working. In part to do the trials because they needed to have enough infected people to be able to do the trials, ironically enough. </p>
<p>So there are many countries that are really behind Cuba and that will help them produce even faster. It’ll enable Cuba to go back to some sort of normalcy, which will enable it to restart its economy. And tourism will be able to start, which is a big moneymaker for Cuba. </p>
<p>Dan: So that’s great for Cuba, but what about other countries in Latin America. Civil rights groups around the world are calling on companies or governments with successful vaccines to waive licences that prevent other manufacturers from producing vaccines, basically to share the intellectual property rights. I asked Jennifer if Cuba will allow other companies or places to make their vaccines. </p>
<p>Jennifer: Cuba has not yet made an official statement about this. What we do know is that Cuba has offered technology transfer, which means knowledge about the capacity to make vaccines, and also pharma supplies, to the country of Ghana. We know that Argentina is looking to collaborate to help Cuba produce its vaccine so that it can use it. We know that in the past what Cuba has done with its doctors, its famous Henry Reeve Brigades, that they typically send those brigades to poor countries for free and they charge for countries who can afford it.</p>
<p>Dan: Cuba’s push to make it’s own vaccine has benefits both internally, but also on the geopolitical map. Like the name of one of its vaccine candidates says, it’s given Cuba sovereignty. To understand more about where Cuba’s vaccine efforts fit into the complicated global politics of COVID-19, I called up to Peter Hotez. </p>
<p>Peter: I’m a professor of paediatrics and molecular virology at Baylor College of Medicine where I also co-direct the Texas Children’s Center for Vaccine Development. We adopted a coronavirus vaccine program about a decade ago. We’ve developed several coronavirus vaccines, and now one for COVID-19 that’s being scaled up for production in India, going into phase 3 clinical trials. </p>
<p>Dan: Peter also has a long-term interest in the geopolitics of vaccines. </p>
<p>Peter: Vaccines are such powerful tools of public health that they become potentially very important instruments of foreign policy. </p>
<p>Dan: He recently wrote a book called <a href="https://jhupbooks.press.jhu.edu/title/preventing-next-pandemic">Preventing the Next Pandemic</a>. It describes what he sees as a decline in global cooperation on vaccine programmes over the past few years. The Covax project aside, he sees this lack of a global strategy playing out during the coronavirus pandemic too.</p>
<p>Peter: Right now you’re clearly seeing haves and have-nots, so the US the UK, some western European countries and Israel have looked after themselves and the rest of the world, not so much. And that’s going to have a lot of implications.</p>
<p>Dan: This unequal distribution of access to vaccines could give the small country of Cuba a lot of leverage to throw around if it does achieve vaccine sovereignty.</p>
<p>Peter: I haven’t followed their vaccine too closely, but the hope is that they work with PAHO, the Pan-American Health Organization, in the western hemisphere and WHO to go through who pre-qualification. And at that point then they can start exporting vaccine or providing it to the Covax sharing facility. That would be the best ideal outcome, I think, and not do what the Russians have done, which is this very transactional encounters with countries, ‘cause that has a lot of downside implications. They’re doing these kind of one-on-one arrangements in this unilateral negotiation. And I think that’s odd and also a lot of these countries adequate pharmacovigilance systems in place. </p>
<p>Dan: The pandemic had exposed significant shortfalls in the private sector focused system of global vaccine development and production. </p>
<p>Peter: This insistence that the multinational pharmaceutical companies can do everything. It’s not working. I mean, the multinational companies have an important role of course, but we need redundancy in the system. We need to have the ability to develop vaccines locally in Africa, expand capacity in Latin America and the Middle East, and in Asia.</p>
<p>Dan: Peter says one way small countries can break their dependency on multinational companies is to basically invest in their own capacity to make vaccines and other drugs. </p>
<p>Peter: Cuba definitely punches above its weight through the Instituto Finlay and, and other organisations. And I think that’s great. We need better capacity. And so what’s happened is a number of organisations have got together and branded themselves as the developing country vaccine manufacturers network. And it includes Cuba, it includes Brazil and includes India of course. India is probably the most advanced in terms of this concept. But we need more of that. </p>
<p>Dan: All of this would require serious investment, and that needs to come from the world’s biggest economies. It won’t be a quick fix to the manufacturing bottlenecks and equality issues surrounding COVID vaccines. But Peter says that’s not really the point. </p>
<p>Peter: We won’t have it in time for this pandemic, but the other pandemics will surely follow. And I think that would be a very productive investment in terms of encouraging security.</p>
<p>Dan: It’s quite possible that little Cuba, could succeed in producing an effective COVID-19 vaccine quickly and cheaply. If this happens, it could really poke a hole in the status quo of the global vaccine and broader biotech ecosystem that keeps power concentrated in wealthy nations. Jennifer Hosek summed it up nicely. </p>
<p>Jennifer: I was thinking about that famous metaphor of the fish and the fishing pole.</p>
<p>Dan: You know the one. Give a man a fish and you feed him for a day. Teach that person how to fish and you feed them for a lifetime. Today though, the idea doesn’t seem to be teach someone how to fish, it’s more teach them how to make a fishing pole. Or in this case, a vaccine. </p>
<p>Jennifer: And so the US is now going to give away it’s extra fish before the fish rot as it were, but actually people around the world know how to make fishing poles and fish in order to catch their own fish. But the many rich countries and big pharma are disallowing them from making those fishing poles and feeding themselves, you know, vaccinating themselves.</p>
<p>And Cuba definitely is a counterexample to that because it’s showing us how a country that uses its resources wisely can organise to catch its own fish and not wait for the castoffs of big pharma, and not also spend its hard-earned money to buy vaccines when it can make it itself. </p>
<p>Gemma: This hunt for vaccine sovereignty is like the holy grail of the early 2020s, isn’t it?</p>
<p>Dan: Vaccines are power, both locally – go to the pub, get a beer – or on the global stage. It would be huge for Cuba to get its own vaccine.</p>
<p>You can read a <a href="https://theconversation.com/the-scene-from-cuba-how-its-getting-so-much-right-on-covid-19-155699">story that Jennifer Hosek has written for The Conversation</a> about the situation in Cuba by clicking the link in the shownotes. You can also follow the latest expert analysis on developments in coronavirus vaccines on our site.</p>
<p>Gemma: For our next story we’re talking about the big decisions that we all have to make in our lives. So Dan, tell me if you made any big decisions recently?</p>
<p>Dan: Yeah, I guess so. I decided to move back across the country to California after having lived on the east coast for a while.</p>
<p>Gemma: You know it’s funny. Sometimes you know that a decision that you’re about to make will be a big one, that it will change the course of your life. But sometimes you make a decision pretty quickly and realise afterwards just how big a choice it was. So to find out more about the process of making these kinds of decisions, I called up a psychologist.</p>
<p>Adrian: My name is Adrian Camilleri. I’m a consumer psychologist. I work at the University of Technology Sydney, and I’m interested in how people make judgement and decisions. </p>
<p>Gemma: Adrian’s <a href="https://theconversation.com/i-asked-hundreds-of-people-about-their-biggest-life-decisions-heres-what-i-learned-154885">recent research</a> was all sparked by a question that he used to ask people at dinner parties. </p>
<p>Adrian: So at dinner parties, I tend to come prepared. And one of my favourite questions to ask at these events is how many of your life’s ten biggest decisions do you think you’ve already made? And this is a question that usually gets a good conversation going because people start to reflect on, “OK, well, what is a big decision and how many have I made so far? And what are the future big decisions coming down the road?” But I thought that maybe I could ask this question in a more scientific way. So I started to put together a questionnaire. And my goal was really to try to understand, well, what are life’s biggest decisions. When do they occur? How do people make these big decisions? Retrospectively, how do they evaluate those big life decisions, and how accurate are people at predicting their future big life decisions?</p>
<p>Gemma: Really interesting stuff. So tell us how you went about doing this. </p>
<p>Adrian: Yeah. So I started to put the questionnaire together in 2019. So first I asked people to tell me about their ten biggest past decisions. The second part of the questionnaire asked people to make predictions about their biggest decisions that are going to happen down the road. And then finally, I asked participants to fill in a number of different questionnaires that measure things like life satisfaction, their decision-making style, impulsiveness, personality, risk tolerance, all of these different individual different variables. So people had an opportunity to type into a box the details of that decision, but then they were asked to categorise those big decisions into some predetermined categories. </p>
<p>But there were also some followup questions. So things like how much time did you spend thinking about the decision before you made it? How much advice did you seek from others? Was it a more intuitive or analytical type decision? And then finally I asked participants to judge in retrospect, whether it was a good or bad decision.</p>
<p>Gemma: Who were you targeting it at?</p>
<p>Adrian: I was looking for an even split of males and females. So I was looking for about 50:50 in every age decile. So I wanted 100 people in their 20s another hundred in their 30s, 40s, 50s, 60s to 70s. So all up in the end, I had 657 people complete the initial study and these participants were dispersed around the United States and they were roughly consistent with the population distribution in the states.</p>
<p>Since that initial survey was completed, I actually built a website that put a much simpler version of the survey up online. That’s located at <a href="https://tenbiggestdecisions.com/">tenbiggestdecisions.com</a> and thousands of people have now filled in that survey. </p>
<p>Gemma: Tell us, what were the kinds of some of the big life decisions that people revealed to you in this process?</p>
<p>Adrian: There were some fun stories in there of people, especially those who are older, doing fun things in the 50s and 60s, driving around the world. But the most commonly mentioned big life decisions are those that won’t surprise you. So starting a new job, getting married, pursuing a degree, having a child, relocating – so moving to a new state – buying a home. </p>
<p>But then there was some decisions that were – when they did occur, which was not that often in some cases – they were always right near the top of that ranking. And so these included ending a life. So this might be perhaps aborting a pregnancy. It could also relate perhaps to ailing parents, maybe who are on life support. But there was also some things up there like pursuing religion, or pursuing a philosophy. These got rated as quite important as well. </p>
<p>Gemma: So they might be rare, but they’re incredibly important to the person taking them?</p>
<p>Adrian: Exactly. </p>
<p>Gemma: So you’ve gone through so what are some of the biggest ones, but what do the results show about how people look back on certain decisions more positively or negatively?</p>
<p>Adrian: Yeah so for every decision that my participants mentioned, the final question was in retrospect, how do you evaluate that decision? Was it a good or a bad decision? And a couple of categories that stood out. The first were the self-destructive decisions, these include things like committing a crime and starting an addiction. So these decisions stood out as being quite different from the rest in that the majority of participants judge these as bad decisions. The other category that stood out were the self-developmental decisions. So these include things like starting a hobby or learning a new skill, travelling, pursuing a religion or a new philosophy. So these self-developmental decisions, the vast majority of participants indicated that these were good decisions.</p>
<p>Gemma: And are there any other trends that emerged in the way people evaluated or described the big decisions? </p>
<p>Adrian: There was two categories that stood out and again. It’s the self-destructive and the self-developmental categories. And when you look at these in terms of time spent thinking, the self-destructive decisions were uncommonly short in how much time was spent thinking. So the most commonly mentioned response was just seconds before engaging in whatever self-destructive activity that was. </p>
<p>And in contrast, if you look at the self-developmental decisions, these tended to be the ones that individuals spent the most time thinking about. So many people indicated they spent years thinking about the decision before they actually engaged in it. </p>
<p>Gemma: And I’m interested in that age question. So were there decisions that say younger people were more likely to have talked about than older people?</p>
<p>Adrian: So career-related decisions definitely increased over time and they actually peaked for people in their 60s. And that might be surprising for some people, but actually the final decision that one makes in their career is a huge one and that’s when to retire. </p>
<p>Other decisions that increase over time were finance-related decisions. So again, people tend to accumulate money, resources, and then they have to think about making decisions about these as they get older, including putting them in a will, which is also another big life decisions that happens later in life. We can also see increase in family-related decisions. </p>
<p>Gemma: You started this by asking people how many of their big decisions they think they have left. So was your data able to pull that out?</p>
<p>Adrian: Definitely. I got to ask my favourite dinner party question. What the results showed was that on average 20-year-olds tended to believe that they had already made three of their life’s biggest decisions.</p>
<p>Gemma: Three of ten. </p>
<p>Adrian: Three three of ten, that’s right. So it could have been maybe education-related decisions, maybe they’d had their first love. Maybe they’d moved already. The mid-point, the five decision point was at around age 44-years-old, that people kind of imagined that they had made half of their big life decisions.</p>
<p>And what was most interesting to me, I think, was looking at those who were older in the sample. So for example, those who were 70-years-old, they estimated that they’d made a little less than seven of their ten biggest decisions. So there were still three big life decisions coming. And when you started to look closely at some of the big life decisions that do happen later in life, you do start to realise that actually, there are a number of big decisions that keep coming up, whether you know, some people get married young, but then a lot of people get remarried when they’re older. </p>
<p>Gemma: What advice, drawing on all this analysis that you’ve done so far on the data that you’ve collected, would you give people on making big decisions in their lives? </p>
<p>Adrian: I guess the first thing to recognise is that, well, first big life decisions are front-loaded. So they happen most for those who are aged between say 16 and 35. But, they still occur for those of all ages. So, I guess keep an open mind to future big decisions and also don’t maybe put too much pressure on yourself when making current big decisions. I know they feel massive at the time, but in retrospect, sometimes they’re not as big. </p>
<p>Another thing that stood out was that there’s a lot of experience out there, that a decision-maker can utilise the wisdom from. So speaking to others and learning from those who have come before, I think are great options for those who are making big life decisions. The research that I conducted also suggests that taking your time is a good way to lead to a good decision, but also avoiding the burden of obligation. So there were some results suggesting that obligation-induced decisions led to poorer outcomes, and also using a more analytical approach rather than relying on pure intuition was more likely to lead to a positive outcome.</p>
<p>And in fact, in this regard, there’s some research related to regret and one way to avoid feelings of regret is to have very good justification for your decisions today. So that even if things turn out poorly down the road, you can turn back and think, “You know what? At the time, given what I knew about the situation, I made a good decision.”</p>
<p>And finally, I think there are some decisions that are very likely going to impact on your life satisfaction. So keep this in mind. So these self-destructive decisions that I’ve mentioned, like engaging in crime and taking up an addiction, these are very likely to lead, to decreases in life satisfaction. And I think the scary thing about these decisions is that they’re made in a fraction of a moment, but they actually tend to have very long-lasting consequences and put one on a treacherous life path. </p>
<p>On the flip side, self-developmental decisions, such as, you know, taking control of your life, pouring yourself into a pursuit or project, these tend to be associated with increased life satisfaction. So, although it can be hard to sometimes find the time for these non-essential, big life decisions, I think your future self will thank you. </p>
<p>Gemma: That’s some great advice there. </p>
<p>Adrian: You’re welcome. Thank you for having me.</p>
<p>Gemma: Since I interviewed Adrian, I’ve been asking some of my friends his question. How many of your life’s big decisions do you think you’ve already taken? It’s a really good conversation starter, I recommend it. You can read more about Adrian’s research by clicking on a link <a href="https://theconversation.com/i-asked-hundreds-of-people-about-their-biggest-life-decisions-heres-what-i-learned-154885">to the story</a> that he wrote in the show notes. </p>
<p>Dan: Now, to end the show, we’ve got some recommended reading from one of our colleagues in New Zealand. </p>
<p>Finlay: Hi, this is Finlay Macdonald. I’m one of the two editors in New Zealand and I’m based in Auckland. I have a couple of recommended articles that we’ve recently published and the first one is something <a href="https://theconversation.com/nzs-hate-speech-proposals-need-more-detail-and-wider-debate-before-they-become-law-159320">I worked on with legal scholar, Eddie Clarke from Victoria University in Wellington</a>. So this is quite a long-running and important story in New Zealand and it goes back to the terrorist attacks on two mosques in Christchurch in 2019. So one of the official responses to that atrocity has been to propose new hate speech laws. And we think there’s going to be a heated debate later in the year between proponents of such laws and free speech advocates who worry about the state interfering in our right to say and think what we want.</p>
<p>But the first challenge of course, is to understand what might change if those proposals became law. As Eddie explains, it could well tighten up definitions of hate speech, but broaden their application in the process, so there’s a real risk of overreach if we don’t get it right.</p>
<p>The second article I’m recommending is very different, but still kiwi, although in this case, the bird and our national symbol. Specifically <a href="https://theconversation.com/forensics-and-ship-logs-solve-a-200-year-mystery-about-where-the-first-kiwi-specimen-was-collected-158410">how the kiwi was very first seen, identified and studied by Europeans</a>. The authors, Paul Scofield and Vanesa De Pietri, from Canterbury University have unravelled what until now was a 200-year-old mystery about how this sadly dead kiwi eventually made it to England. It’s a remarkable tale, told through historical records, ships’ logs from the early 1800s and modern forensic DNA techniques, which tell us as much about early colonial scientific activity as they do about the bird itself. Hope you enjoy it.</p>
<p>That’s all from me for now. Happy reading.</p>
<p>Gemma: Finlay Macdonald there in Auckland. </p>
<p>That’s it for this week. Thanks to all the academics who’ve spoken to us for this episode. And to The Conversation editors Lee-Anne Goodman, Michael Lucy, Finlay Macdonald and Stephen Khan. And thanks to Alice Mason, Imriel Morgan and Sharai White for our social media promotion. </p>
<p>Dan: You can find us on Twitter <a href="https://twitter.com/TC_Audio">@TC_Audio</a> or on Instagram at <a href="https://www.instagram.com/theconversationdotcom/?hl=en">theconversationdotcom</a> or email us at podcast@theconversation.com. And if you want to learn more about any of the things we talked about on the show today, there are links to further reading in the <a href="https://theconversation.com/cubas-race-to-make-its-own-coronavirus-vaccine-podcast-160324">show notes</a> where you can also find a link to sign up to our <a href="https://theconversation.com/newsletter?utm_campaign=PodcastTCWeekly&utm_content=newsletter&utm_source=podcast">free daily email</a>.</p>
<p>Gemma: The Conversation Weekly is co-produced by Mend Mariwany and me, Gemma Ware, with sound design by Eloise Stevens. Our theme music is by Neeta Sarl. </p>
<p>Dan: And I’m Dan Merinio. Thanks so much for listening.</p><img src="https://counter.theconversation.com/content/160551/count.gif" alt="The Conversation" width="1" height="1" />
A transcript of episode 14 of The Conversation Weekly podcast, including how people make their life’s biggest decisions.Gemma Ware, Head of AudioDaniel Merino, Associate Breaking News Editor and Co-Host of The Conversation Weekly PodcastLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1603452021-05-07T00:54:46Z2021-05-07T00:54:46ZWhat’s the Valneva COVID-19 vaccine, the French shot that’s supposed to be ‘variant proof’?<figure><img src="https://images.theconversation.com/files/399120/original/file-20210506-14-ssjrin.jpg?ixlib=rb-1.1.0&rect=0%2C4%2C1000%2C658&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/valneva-covid19-vaccine-concept-finger-pointing-1950918379">mundissima/www.shutterstock.com</a></span></figcaption></figure><p>A COVID-19 vaccine from French company Valneva has yet to complete clinical trials. But it has <a href="https://www.news.com.au/national/australia-in-talks-with-french-firm-valneva-about-importing-vaccine/news-story/bcd4d56629b5469311b1d9a5db6edcc3">caught the eye</a> of governments in the UK, <a href="https://twitter.com/ReutersWorld/status/1388201550938529799">Europe</a> and Australia. </p>
<p>One of the vaccine’s main selling points is its apparent ability to mount a more general immune response against SARS-CoV-2, the virus that causes COVID-19, rather than rely on the <a href="https://theconversation.com/revealed-the-protein-spike-that-lets-the-2019-ncov-coronavirus-pierce-and-invade-human-cells-132183">spike protein</a> to do this.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1388352479985905664"}"></div></p>
<p>This means the vaccine is more likely to be effective against the type of virus variants we’ve already seen emerging, and may emerge in the future. <a href="https://www.scmp.com/news/world/europe/article/3131661/french-firms-more-variant-proof-coronavirus-vaccine-could-help">Some reports</a> describe it as “<a href="https://medium.com/technicity/phase-3-trials-on-a-new-variant-proof-vaccine-begin-9f52225e7350">variant proof</a>”. </p>
<p>The hope is vaccines using this technology would be able to provide protection for longer, rather than keep being reformulated to get ahead of these new variants.</p>
<h2>How does it work?</h2>
<p>Valneva’s vaccine, called VLA2001, is based on tried and tested vaccine technology. It’s the technology used in the vaccine against <a href="https://www.jstor.org/stable/24858956">poliovirus</a> and in some types of <a href="https://www.cdc.gov/flu/prevent/quadrivalent.htm">flu vaccines</a>. And the company already has a commercially available <a href="https://preventje.com/hcp/what-is-ixiaro/">Japanese encephalitis</a> vaccine based on the same technology.</p>
<p>VLA2001 uses an <a href="https://www.who.int/news-room/feature-stories/detail/the-race-for-a-covid-19-vaccine-explained">inactivated version of the whole virus</a>, which cannot replicate or cause disease.</p>
<p>The virus is inactivated using a chemical called <a href="https://pubchem.ncbi.nlm.nih.gov/compound/beta-Propiolactone">beta-propiolactone or BPL</a>. This is <a href="https://www.tandfonline.com/doi/full/10.1586/erv.12.38">widely used</a> to inactivate other viruses for vaccines. It was even used to make <a href="https://www.liebertpub.com/doi/full/10.1089/vim.2010.0028?casa_token=jNYegUijdDkAAAAA%3AQfR_VQ4OjQeI70ajPwgEZb_2lWASqd2Mm5xMcj9aDKYOS0FFAB344DzrqW7g-lmaTeKDW-T8oJI">experimental versions</a> of vaccines against SARS-CoV, the virus that caused <a href="https://www.cdc.gov/sars/about/fs-sars.html">SARS (severe acute respiratory syndrome)</a>.</p>
<p>This type of inactivation is expected to preserve the structure of the viral proteins, as they would occur in nature. This means the immune system will be presented with something similar to what occurs naturally, and mount a strong immune response.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/from-adenoviruses-to-rna-the-pros-and-cons-of-different-covid-vaccine-technologies-145454">From adenoviruses to RNA: the pros and cons of different COVID vaccine technologies</a>
</strong>
</em>
</p>
<hr>
<p>After being inactivated, the vaccine would be highly purified. Then, an adjuvant (an immune stimulant) is added to induce a strong immune response.</p>
<p>VLA2001 isn’t the first inactivated vaccine against COVID-19. Leading COVID-19 inactivated vaccines, such as those developed by Sinopharm and Bharat Biotech, have been <a href="https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html">approved for use</a> in China and received emergency approval in other countries, including India.</p>
<p>However, VLA2001 is the only COVID-19 vaccine candidate using whole inactivated virus in clinical trials in the UK and in mainland Europe.</p>
<h2>What are the benefits we know so far?</h2>
<p>This approach to vaccine development presents the immune system with all of the structural components of the SARS-CoV-2 virus, not just the spike protein, as many other COVID-19 vaccines do. </p>
<p>So Valneva’s vaccine is thought to produce a more broadly protective immune response. That is, antibodies and cells of the immune system are able to recognise and neutralise more pieces of the virus than just the spike protein. </p>
<p>As a result, Valneva’s vaccine could be more effective at tackling emerging COVID-19 virus variants and, if approved, play a useful role as a booster vaccine. </p>
<p>Valneva’s vaccine can be stored at <a href="https://valneva.com/research-development/covid-19-vla2001/">standard cold-chain conditions (2-8°C)</a> and is expected to be given as two shots.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/uk-south-african-brazilian-a-virologist-explains-each-covid-variant-and-what-they-mean-for-the-pandemic-154547">UK, South African, Brazilian: a virologist explains each COVID variant and what they mean for the pandemic</a>
</strong>
</em>
</p>
<hr>
<h2>How about results from clinical trials?</h2>
<p><a href="https://clinicaltrials.gov/ct2/show/NCT04671017?term=valneva&draw=3&rank=5">According to</a> <a href="https://valneva.com/press-release/valneva-reports-positive-phase-1-2-data-for-its-inactivated-adjuvanted-covid-19-vaccine-candidate-vla2001/">the company</a>, no safety concerns or serious adverse events were associated with VLA2001 in early-stage clinical trials. </p>
<p>VLA2001 was given as a low, medium or high dose in these trials with <a href="https://clinicaltrials.gov/ct2/show/NCT04671017?term=valneva&draw=3&rank=5">all participants</a> in the high-dose group generating antibodies to the virus spike protein. </p>
<p>One measure of immune response in the high-dose group after completing the two doses indicated antibody levels were, after two weeks, at least as high as those seen in patients naturally infected with SARS-CoV-2.</p>
<p>Interestingly, VLA2001 induced immune responses against a number of virus proteins (including the spike protein) across all participants, an encouraging sign the vaccine can provide broad protection against COVID-19.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1389505076708864003"}"></div></p>
<p>The vaccine has since advanced to <a href="https://valneva.com/press-release/valneva-initiates-phase-3-clinical-trial-for-its-inactivated-adjuvanted-covid-19-vaccine-candidate-vla2001/">phase 3 clinical trials</a> in the UK. The trial, which started in April 2021, will compare its safety and efficacy <a href="https://www.globenewswire.com/news-release/2021/04/21/2214528/0/en/Valneva-Initiates-Phase-3-Clinical-Trial-for-its-Inactivated-Adjuvanted-COVID-19-Vaccine-Candidate-VLA2001.html">with the AstraZeneca vaccine</a>. </p>
<p>The phase 3 trial is expected to be completed by the northern hemisphere’s <a href="https://www.bloomberg.com/news/articles/2021-04-29/a-french-biotech-says-inactivated-vaccines-are-the-way-to-fight-covid-variants">autumn this year</a>. And if successful, would be submitted for regulatory approval after that.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/a-single-vaccine-to-beat-all-coronaviruses-sounds-impossible-but-scientists-are-already-working-on-one-156373">A single vaccine to beat all coronaviruses sounds impossible. But scientists are already working on one</a>
</strong>
</em>
</p>
<hr>
<h2>Who’s interested?</h2>
<p>Despite phase 3 clinical trials only just starting, the UK government has <a href="https://www.news.com.au/national/australia-in-talks-with-french-firm-valneva-about-importing-vaccine/news-story/bcd4d56629b5469311b1d9a5db6edcc3">pre-ordered</a> more than <a href="https://valneva.com/press-release/valneva-announces-uk-government-exercise-of-option-for-40-million-doses-of-its-inactivated-adjuvanted-covid-19-vaccine/">100 million doses</a> of the vaccine from Valneva, with the option of buying more down the track. If trials prove successful and pass regulatory approval, this means the vaccine could be used as a booster in time for this year’s northern hemisphere’s winter.</p>
<p>Australia <a href="https://www.news.com.au/national/australia-in-talks-with-french-firm-valneva-about-importing-vaccine/news-story/bcd4d56629b5469311b1d9a5db6edcc3">has confirmed</a> it’s also in talks with Valeneva about importing the vaccine. Some countries in Europe are also <a href="https://www.reuters.com/world/europe/exclusive-some-eu-nations-still-want-valneva-covid-19-vaccine-deal-sources-2021-04-30/?taid=608c4f0e12d1d500012373d2&utm_campaign=trueAnthem:+Trending+Content&utm_medium=trueAnthem&utm_source=twitter">reportedly keen</a> to strike a deal.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1388201550938529799"}"></div></p>
<p>As new cases of COVID-19 increase globally, we’ll continue to see new viral variants emerge that threaten to escape the protection existing vaccines offer.</p>
<p>Already, we are seeing vaccines from companies <a href="https://www.theguardian.com/world/2021/may/05/tweaked-moderna-vaccine-neutralises-covid-variants-in-trials">such as</a> <a href="https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-positive-initial-booster-data-against-sars-cov">Moderna</a> and <a href="https://www.wsj.com/articles/covid-19-vaccines-targeting-multiple-strains-are-in-the-works-11615374007">Novavax</a> begin to reformulate their spike protein-based vaccines to get ahead of emerging variants.</p>
<p>So Valneva’s vaccine, with the potential to elicit a more broadly protective immune response, may prove to be a useful tool to combat the rise of the virus and its mutations. However, whether the vaccine is really “variant proof” or merely less affected by emerging variants remains to be seen.</p><img src="https://counter.theconversation.com/content/160345/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Adam Taylor receives funding from the Australian National Health and Medical Research Council. </span></em></p>It sounds too good to be true, a vaccine that can protect against future virus variants. But governments around the world are keen to learn more.Adam Taylor, Early Career Research Leader, Emerging Viruses, Inflammation and Therapeutics Group, Menzies Health Institute Queensland, Griffith UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1557142021-02-23T19:11:30Z2021-02-23T19:11:30ZHow do we know the COVID vaccine won’t have long-term side-effects?<figure><img src="https://images.theconversation.com/files/385476/original/file-20210222-13-7imnr3.jpg?ixlib=rb-1.1.0&rect=0%2C8%2C5991%2C3979&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>As Australia’s COVID-19 vaccine rollout begins this week, many people still have questions about the <a href="https://www.abc.net.au/news/health/2021-01-27/covid-vaccine-safety-questions/13089036">safety of COVID-19 vaccines</a>, both in the short and long term.</p>
<p>As vaccine experts, we hear these concerns all the time, and it’s normal to have questions about a vaccine.</p>
<p>The good news is that scientists have already been testing COVID-19 vaccines for months. For starters, serious side-effects are very, very rare. And, together with what we know about previous vaccines, if side-effects are going to occur, they usually happen within a few months after getting a vaccine. This is why international medical regulators, including Australia’s Therapeutic Goods Administration (TGA), require the first few months of safety data before approving new vaccines. This, plus information coming from vaccine recipients in the northern hemisphere, gives us confidence that COVID-19 vaccines are safe.</p>
<p>In fact, most side-effects occur within the first one or two days. And most of these are minor, such as pain at the injection site, fatigue or fever — which are signs your immune system is building a response against the thing you’ve been vaccinated against.</p>
<h2>What do we know about long-term side effects?</h2>
<p>Since December, <a href="https://ourworldindata.org/covid-vaccinations">more than 200 million people</a> have received at least one dose of a COVID-19 vaccine worldwide — more than the total number of people who have been infected with the virus (<a href="https://www.worldometers.info/coronavirus/">112 million</a>).</p>
<p>Given the sheer number of vaccines administered to date, common, uncommon and rare side-effects would have been detected by now. What’s more, we’ve been testing these vaccines in clinical trials since mid-2020, and both the Pfizer and AstraZeneca vaccines have shown excellent safety results.</p>
<p>This gives us confidence the vaccines that’ll be used around Australia are safe.</p>
<p>We’ve also seen some people raise concerns online about mRNA vaccines, such as the Pfizer-BioNTech vaccine, being a <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/mrna.html">“new” technology</a>. mRNA (or “messenger” RNA) is found in all living cells. <a href="https://www.gavi.org/vaccineswork/will-mrna-vaccine-alter-my-dna">mRNA is a message</a> that tells cells how to make proteins that trigger the immune response inside the body. That immune response is what protects against infection if an individual is exposed to the virus. mRNA is not the same as DNA (your genes), and it cannot combine with our DNA to change our genetic code. <a href="https://www.forbes.com/sites/victoriaforster/2021/01/11/covid-19-vaccines-cant-alter-your-dna-heres-why/?sh=cfed61224911">mRNA vaccines do not affect or interact with DNA</a> in any way. So we can be assured there’ll be no long-term DNA-altering effects from these vaccines.</p>
<p>What’s more, checking the safety of the vaccines doesn’t just stop after they’ve been registered for use. Once a vaccine has been introduced, <a href="https://www.immune.org.nz/vaccines/vaccine-safety/safety-monitoring">ongoing monitoring</a> of its safety is a crucial part of the vaccine development process. </p>
<p>Australia has a <a href="https://theconversation.com/covid-vaccines-have-been-developed-in-record-time-but-how-will-we-know-theyre-safe-153888">robust system for this ongoing monitoring</a>. The system was established to detect any unexpected side-effects from vaccines (if they occur) and ensure they’re investigated promptly. This type of monitoring is standard practise in Australia for vaccines. The data about COVID-19 vaccination collected in these surveillance systems will be published weekly on the <a href="https://www.tga.gov.au/communicating-covid-19-safety-information">TGA website</a>. This should reassure Australians that if there’s a new serious side-effect, we will know about it, communicate it, and act on it quickly.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/covid-vaccines-have-been-developed-in-record-time-but-how-will-we-know-theyre-safe-153888">COVID vaccines have been developed in record time. But how will we know they're safe?</a>
</strong>
</em>
</p>
<hr>
<p><a href="https://www.cdc.gov/vaccinesafety/concerns/concerns-history.html">Withdrawal of vaccines</a> after introduction to the general population is a very rare event.
In the United States, a rotavirus vaccine called <a href="https://www.cdc.gov/mmwr/preview/mmwrhtml/mm4843a5.htm">Rotashield</a> led to a small increase in the number of small intestinal blockages. This prompted its withdrawal in the late 1990s. In Australia, an <a href="https://www.tga.gov.au/alert/seasonal-flu-vaccine-investigation-febrile-reactions-young-children-following-2010-seasonal-trivalent-influenza-vaccination">increased risk of febrile seizures</a> in young children following a specific influenza vaccine was identified in 2010. It was subsequently withdrawn from use in that age group, and we now vaccinate with a different, <a href="https://www.ausvaxsafety.org.au/safety-data/influenza-vaccine">safer flu vaccine</a>. This vaccine is <a href="https://immunisationhandbook.health.gov.au/vaccine-preventable-diseases/influenza-flu">no longer available in Australia</a>, and has been subsequently reformulated. </p>
<p>Both of these side-effects were observed within weeks of vaccination.</p>
<p>We now have improved monitoring systems in Australia to detect such serious side-effects <a href="https://bmjopen.bmj.com/content/10/2/e031851">even sooner</a>, in the general population after clinical trials, than we did a decade ago.</p>
<h2>But what about short-term side-effects?</h2>
<p><strong>Pfizer-BioNTech COVID-19 vaccine</strong></p>
<p>The expected side-effects of the Pfizer vaccine have been reported from <a href="https://www.nejm.org/doi/pdf/10.1056/NEJMoa2034577?articleTools=true">trials</a> involving roughly 43,000 participants aged 16 years and older from the US, Argentina, Brazil and South Africa. Half of the participants received the Pfizer vaccine and half received a placebo. And as part of COVID-19 vaccine rollouts around the world, <a href="https://ourworldindata.org/covid-vaccinations">millions of people</a> have already been given this vaccine since December, meaning we have safety data now from both clinical trials and two months of “real world” vaccination. </p>
<p>For those receiving this vaccine in the large clinical trials which <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-conclude-phase-3-study-covid-19-vaccine">started in July 2020</a>, <a href="https://www.fda.gov/media/144246/download">about 80%</a> have reported pain at the injection site. Other common side-effects included fatigue, headache, muscle pain, chills, joint pain and fever.</p>
<p>These were most often reported one or two days after the day of vaccination, and typically only lasted about one day. While some vaccine recipients may need a day off work due to some of these side-effects, this does not indicate the vaccine is unsafe. </p>
<p>In trials, no difference was seen in the rate of severe side-effects between the Pfizer vaccine and placebo. Early in the US program, <a href="https://www.cdc.gov/mmwr/volumes/70/wr/mm7002e1.htm">21 cases of anaphylaxis</a> were reported. It’s <a href="https://www.cdc.gov/mmwr/volumes/70/wr/mm7002e1.htm">estimated</a> anaphylaxis occurs at a rate of 11 in every one million recipients (0.0011%) of the Pfizer COVID-19 vaccine. Most occurred within 15 minutes, and all patients recovered. This is why it’s a good idea though to remain at the vaccine clinic for up to <a href="https://immunisationhandbook.health.gov.au/vaccination-procedures/after-vaccination">15 minutes</a> after vaccination so that treatment and care can be provided if necessary. </p>
<p>A <a href="https://www.tga.gov.au/media-release/investigation-reveals-no-specific-risk-covid-19-vaccinations-elderly-patients">further concern was raised in January</a>, after the death of 30 very frail elderly patients in Norway after receiving the Pfizer-BioNTech COVID-19 vaccine. But <a href="https://www.ema.europa.eu/en/documents/covid-19-vaccine-safety-update/covid-19-vaccine-safety-update-comirnaty-january-2021_en.pdf">investigation by the European regulator</a> concluded these weren’t related to the vaccine, but rather to underlying conditions present before vaccination. </p>
<p><strong>Oxford-AstraZeneca COVID-19 vaccine</strong></p>
<p>This vaccine has been tested in ongoing trials with around 55,000 participants from the <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/fulltext">United Kingdom, Brazil, South Africa</a> and <a href="https://clinicaltrials.gov/ct2/show/NCT04516746">the US</a>. About half received the Oxford-AstraZeneca vaccine and half a placebo. <a href="https://www.gov.uk/government/publications/coronavirus-covid-19-vaccine-adverse-reactions/coronavirus-vaccine-summary-of-yellow-card-reporting#annex-1-vaccine-analysis-print">Millions of doses</a> have been already been administered among the general population, particularly in the UK.</p>
<p>Data from four <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/fulltext">clinical trials</a> which commenced in April 2020 in the UK, Brazil and South Africa, show the most common side-effects were pain at the injection site, fatigue, headache and muscle pain. Similar to the Pfizer vaccine, there was no difference in the rate of reported severe side-effects for the vaccine compared with the placebo.</p>
<p>Just 0.7% of <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/fulltext">participants</a> (79 people) from the four clinical trials who received the Oxford-AstraZeneca vaccine reported a serious side-effect after receiving at least one dose, compared with 0.8% (89 people) of those in the placebo group. <a href="https://www.gov.uk/government/publications/coronavirus-covid-19-vaccine-adverse-reactions/coronavirus-vaccine-summary-of-yellow-card-reporting#annex-1-vaccine-analysis-print">No additional safety concerns</a> have been identified since the vaccination program began in the UK.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/should-i-get-a-covid-vaccine-while-im-pregnant-or-breastfeeding-is-it-safe-for-me-and-my-baby-153309">Should I get a COVID vaccine while I'm pregnant or breastfeeding? Is it safe for me and my baby?</a>
</strong>
</em>
</p>
<hr>
<h2>If recommended a COVID-19 vaccine, take it</h2>
<p>With countries continuing to monitor those who have received vaccines, we should be reassured there are no major safety concerns detected for serious side-effects so far. With millions of people vaccinated already, our confidence about the safety of COVID-19 vaccines is very high.</p>
<p>In Australia, and internationally, we have robust systems in place to continually monitor vaccine safety, ensuring Australians can be safely afforded the protection that COVID-19 vaccines are designed to provide.</p><img src="https://counter.theconversation.com/content/155714/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Chris Blyth receives funding from the National Health and Medical Research Council. He is affiliated with the Australasian Society of Infectious Diseases, and is a member of government advisory committees including Australian Technical Advisory Group on Immunisation and COVID-19 Vaccines and Treatment for Australia - Science and Industry Technical Advisory Group.</span></em></p><p class="fine-print"><em><span>Margie Danchin receives funding from the National Health and Medical Research Council, WHO and Commonwealth and State government. She is a member of the Australian Technical Advisory Group on Immunisation COVID-19 Vaccine working group on vaccine safety, confidence and evaluation and chair of the Collaboration on Social Science and Immunisation (COSSI). </span></em></p><p class="fine-print"><em><span>Nicholas Wood receives funding from the NHMRC for a Career Development Fellowship</span></em></p><p class="fine-print"><em><span>Lucy Deng and Samantha Carlson do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Years of vaccine research tells us that, if side effects are going to occur, they normally occur within the first months after getting a vaccine.Samantha Carlson, Post Doctoral Research Officer, Telethon Kids InstituteChristopher Blyth, Paediatrician, Infectious Diseases Physician and Clinical Microbiologist, Telethon Kids Institute, The University of Western AustraliaLucy Deng, Paediatrician, National Centre for Immunisation Research and Surveillance; Clinical Lecturer, Children's Hospital Westmead Clinical School, University of SydneyMargie Danchin, Associate Professor, University of Melbourne, Murdoch Children's Research InstituteNicholas Wood, Associate Professor, Discipline of Childhood and Adolescent Health, University of SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1541602021-02-04T19:10:00Z2021-02-04T19:10:00Z4 things about mRNA COVID vaccines researchers still want to find out<figure><img src="https://images.theconversation.com/files/382170/original/file-20210203-17-xhiwgs.jpg?ixlib=rb-1.1.0&rect=1%2C0%2C997%2C558&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/mrna-chains-contained-modern-coronavirus-vaccine3d-1901812402">from www.shutterstock.com</a></span></figcaption></figure><p>The first mRNA vaccines approved for use in humans — the <a href="https://theconversation.com/how-mrna-vaccines-from-pfizer-and-moderna-work-why-theyre-a-breakthrough-and-why-they-need-to-be-kept-so-cold-150238">Pfizer/BioNTech and Moderna COVID-19 vaccines</a> — are being rolled out around the world.</p>
<p>These vaccines deliver <a href="https://theconversation.com/explainer-what-is-rna-15169">mRNA</a>, coated in lipid (fat), into cells. Once inside, your body uses instructions in the mRNA to make SARS-CoV-2 spike proteins. The immune response <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2034577">protects</a> <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2035389">around 95%</a> of people vaccinated with either vaccine from developing COVID-19.</p>
<p><a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/mrna.html">Such mRNA vaccines</a> have many benefits. They are quick to design, so once the manufacturing platform is set up, mRNA vaccines can be designed to target different viruses, or variants, very quickly. The vaccine manufacturing is also fully synthetic, and doesn’t rely on living cells like chicken eggs, or cultured cell lines. So this technology <a href="https://www.nature.com/articles/nrd.2017.243">is here to stay</a>. </p>
<p>However, there are still issues we need to improve on to help make mRNA vaccines become more practical and affordable for the entire world, not just first-world countries. Here are four areas mRNA vaccine researchers are working on. </p>
<h2>1. How to make them more stable at higher temperatures</h2>
<p>We know mRNA and its lipid coat is relatively <a href="https://www.sciencedirect.com/science/article/pii/S0022354920307851">unstable</a> in a fridge or at room temperature. That’s because RNA is more sensitive than DNA to enzymes in the environment that will degrade it. </p>
<p>To overcome this, researchers are working on testing what happens when different types of additives are included, hoping they will extend the vaccines’ shelf life. These additives have been used in vaccines before and include, for example, small amounts of <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5221800/">common sugars</a>.</p>
<p>Another approach is to freeze-dry mRNA vaccines into a powder for storage. The idea is to then add water to “reconstitute” the vaccine powder before injection. California-based company Arcturus <a href="https://ir.arcturusrx.com/news-releases/news-release-details/arcturus-therapeutics-announces-positive-interim-arct-021-lunar">is trialling</a> this strategy in a phase III clinical trial in Singapore.</p>
<p>CureVac, which is also developing an mRNA COVID-19 vaccine, has already overcome some of these challenges. It has produced a vaccine stable for <a href="https://www.statnews.com/2021/02/03/gsk-joins-forces-with-curevac-to-manufacture-its-covid-19-vaccine-and-to-develop-another/">three months at fridge temperature</a>. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/how-mrna-vaccines-from-pfizer-and-moderna-work-why-theyre-a-breakthrough-and-why-they-need-to-be-kept-so-cold-150238">How mRNA vaccines from Pfizer and Moderna work, why they're a breakthrough and why they need to be kept so cold</a>
</strong>
</em>
</p>
<hr>
<h2>2. How to reduce the amount of vaccine in each shot</h2>
<p>The current mRNA vaccine doses range from <a href="https://www.tga.gov.au/sites/default/files/auspar-bnt162b2-mrna-210125-pi.pdf">30 micrograms</a> (Pfizer/BioNTech) to <a href="https://www.fda.gov/media/144637/download">100 micrograms</a> (Moderna). In phase I clinical trials, <a href="https://www.nature.com/articles/s41586-020-2639-4">lower doses</a> of the Pfizer/BioNTech vaccine were also active.</p>
<p>Could we go lower than this? CureVac has developed a COVID-19 mRNA vaccine with a dose of <a href="https://www.curevac.com/en/2020/11/10/curevac-publishes-detailed-interim-phase-1-data-of-its-covid-19-vaccine-candidate-cvncov/">12 micrograms</a> through a combination of innovations in mRNA sequence and lipid formulations. However, the details of this remain proprietary.</p>
<p>Self-amplifying mRNA is another approach to reduce vaccine doses. Self-amplifying mRNA is engineered to make more copies of itself once delivered into cells. This means only a small initial dose is needed.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/381932/original/file-20210202-19-1dvzp63.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/381932/original/file-20210202-19-1dvzp63.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=463&fit=crop&dpr=1 600w, https://images.theconversation.com/files/381932/original/file-20210202-19-1dvzp63.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=463&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/381932/original/file-20210202-19-1dvzp63.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=463&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/381932/original/file-20210202-19-1dvzp63.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=582&fit=crop&dpr=1 754w, https://images.theconversation.com/files/381932/original/file-20210202-19-1dvzp63.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=582&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/381932/original/file-20210202-19-1dvzp63.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=582&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Self-amplifying and standard mRNA. Theoretically, lower doses are needed with self-amplifying RNA to generate the same antigen levels (Author provided).</span>
</figcaption>
</figure>
<p>Researchers at <a href="https://www.nature.com/articles/s41467-020-17409-9">Imperial College London</a> and <a href="https://www.clinicaltrialsarena.com/news/arcturus-therapeutics-initiate-study/">Arcturus</a> are using this method to develop COVID-19 vaccines, although trials have only recently completed <a href="https://www.clinicaltrialsarena.com/news/arcturus-therapeutics-initiate-study/">phase I stage</a>.</p>
<p>While more research will be needed to understand self-amplifying mRNA vaccines, this could reduce costs, as less material is needed.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/not-sure-about-the-pfizer-vaccine-now-its-been-approved-in-australia-you-can-scratch-these-4-concerns-straight-off-your-list-153719">Not sure about the Pfizer vaccine, now it's been approved in Australia? You can scratch these 4 concerns straight off your list</a>
</strong>
</em>
</p>
<hr>
<h2>3. How to switch from two doses to one</h2>
<p>Current mRNA COVID-19 vaccines need “boosting”. This is where the first injection primes the immune system, then a second one, <a href="https://www.tga.gov.au/sites/default/files/auspar-bnt162b2-mrna-210125-pi.pdf">three</a> to <a href="https://www.fda.gov/media/144638/download">four</a> weeks later, boosts the immune response.</p>
<p>It would be much simpler if a single shot could give the same efficacy. And if COVID-19 remains with us, in the future we will need to boost the immune response regularly, such as with yearly flu vaccines. </p>
<p>In this case, a once-a-year booster shot will be a single injection, rather than the current strategy.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/why-it-takes-2-shots-to-make-mrna-vaccines-do-their-antibody-creating-best-and-what-the-data-shows-on-delaying-the-booster-dose-153956">Why it takes 2 shots to make mRNA vaccines do their antibody-creating best – and what the data shows on delaying the booster dose</a>
</strong>
</em>
</p>
<hr>
<p>Again, self-amplifying mRNA may be useful. Arcturus <a href="https://ir.arcturusrx.com/news-releases/news-release-details/arcturus-therapeutics-announces-positive-interim-arct-021-lunar">announced</a> encouraging results from a single injection of a self-amplifying mRNA vaccine. </p>
<p>In <a href="https://www.biorxiv.org/content/10.1101/2020.09.03.280446v1.full">research involving mice</a>, posted online but not yet formally published in a journal, a single injection of a self-amplifying mRNA vaccine showed a robust immune response.</p>
<p>Another approach was <a href="https://science.sciencemag.org/content/357/6356/1138">developed by researchers at the Massachusetts Institute of Technology</a> for protein vaccines. This uses micro-spheres of polymer that can release the vaccine into the body at day one and day 21. This could “boost” in a single injection. A similar micro-sphere approach could be used with mRNA vaccines. </p>
<h2>4. How to keep ahead of viral variants and have boosters ready</h2>
<p>We know mRNA vaccine technology is well suited to rapidly responding to emerging viral variants. That’s because the chemical and physical properties of mRNA remain the same, even with small sequence changes required to match viral mutants. This means making modified mRNA vaccines for mutants is <a href="https://www.nature.com/articles/nrd.2017.243">quick and simple</a>.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/381940/original/file-20210202-13-v0r4n5.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/381940/original/file-20210202-13-v0r4n5.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/381940/original/file-20210202-13-v0r4n5.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/381940/original/file-20210202-13-v0r4n5.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/381940/original/file-20210202-13-v0r4n5.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=501&fit=crop&dpr=1 754w, https://images.theconversation.com/files/381940/original/file-20210202-13-v0r4n5.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=501&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/381940/original/file-20210202-13-v0r4n5.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=501&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">mRNA vaccines designed for different variants have similar manufacturing and packaging processes. This simplifies the response to emerging mutations, such as the UK and South African (SA) variants (Author provided).</span>
</figcaption>
</figure>
<p>The main hurdle for a varied sequence will be regulatory approval. However, in a recent interview, the US <a href="https://www.ama-assn.org/delivering-care/public-health/fda-director-peter-marks-md-phd-discusses-covid-19-vaccine-safety">Food and Drug Administration suggested</a> mRNA vaccines against mutated versions may be accepted with a small clinical trial (or no trials for future mutations). We don’t know if Australia’s Therapeutic Goods Administration will take a similar approach.</p><img src="https://counter.theconversation.com/content/154160/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Archa Fox receives funding from The Australian Research Council and the National Health and Medical Research Council of Australia. She is affiliated with The Harry Perkins Institute of Medical Research, The RNA Society and the RNA Network of Australia. </span></em></p><p class="fine-print"><em><span>Harry Al-Wassiti receives funding from Monash University and The Medical Research Future Fund (MRFF) to develop mRNA Covid19 vaccine. He collaborates, consults for or works for industry collaborators such as Seqirus, Servier and other biotechnology and governments bodies.</span></em></p>Researchers are already working to improve the current crop of mRNA vaccines. Hopefully this will help them become more practical and affordable for the entire world, not just first-world countries.Archa Fox, Associate Professor and ARC Future Fellow, The University of Western AustraliaHarry Al-Wassiti, Bioengineer and Research Fellow, Monash UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1542322021-01-29T12:47:52Z2021-01-29T12:47:52ZAstraZeneca, Germany and over-65s: how to interpret confusing vaccine data<p>Germany has recently announced that it will not offer the AstraZeneca COVID-19 jab to over-65s due to <a href="https://www.reuters.com/article/us-health-coronavirus-germany-astrazenec/germany-recommends-astrazeneca-covid-19-shot-only-for-under-65s-idUSKBN29X1PY">insufficient data about its efficacy in that age group</a>. </p>
<p>Meanwhile, initial data from Israel seemed to suggest that 14 days after the Pfizer/BioNTech first vaccine dose, patients only had a 33% reduced chance of infection – <a href="https://www.bmj.com/content/372/bmj.n217">disappointingly low according to some reports</a>. But more encouraging data has since emerged showing that after the second dose <a href="https://www.timesofisrael.com/vaccine-found-92-effective-in-israel-in-first-controlled-result-outside-trials/">the vaccine is 92% “effective”</a>.</p>
<p>These stories make headline news and stimulate heated debate as to whether authorities are making the right decisions about which vaccines to use. At a time of great uncertainty and contradictory viewpoints, many are quick to jump on any new data that appears to support their views. But these headline figures can be extremely misleading.</p>
<h2>Germany’s AstraZeneca decision</h2>
<p>The decision by the German <a href="https://www.rki.de/EN/Content/infections/Vaccination/recommandations/recommendations_node.html">Standing Committee on Vaccination (STIKO)</a> not to recommend the Oxford-AstraZeneca vaccination to over-65s is perhaps a case in point. </p>
<p>The original data that regulators in all countries have been looking at, which was <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/fulltext">published in the Lancet</a>, does indeed show fewer trial participants in the over-65s category. </p>
<p>So on one hand the German regulator is correct to say there is not enough data from over-65s. But for others to extrapolate this observation to a conclusion that the vaccine is either ineffective, or dangerous (and thus shouldn’t be given) to this older age group is not appropriate – absence of evidence is not evidence of absence. This decision is more likely to represent a quirk of the way the German regulator works rather than a major medical or scientific concern that should cause concern for other countries.</p>
<h2>Asking the right question</h2>
<p>Research is a complex process, and contrary to the popular saying, interpreting medical research is far trickier than even rocket science. One of the main problems is the difficulty in asking the right question, or working out whether the data being reported actually relates to the question that you (or the politicians) are interested in. Medical research is extremely specific, and it is dangerous to generalise conclusions from studies that are by necessity very precise.</p>
<p>Take, for instance, the difference between “efficacy” and “effectiveness”. Novavax has recently announced an extremely precise <a href="https://ir.novavax.com/news-releases/news-release-details/novavax-covid-19-vaccine-demonstrates-893-efficacy-uk-phase-3">89.3% efficacy</a> for its new COVID-19 vaccine. So what should we make of this – another triumph of medical research or the start of a marketing campaign by the pharmaceutical company?</p>
<p>Here it is important to understand that efficacy relates to the performance of a vaccine under carefully controlled <a href="https://theconversation.com/pfizer-vaccine-what-an-efficacy-rate-above-90-really-means-149849">trial conditions</a>, while effectiveness is the performance under real world conditions. </p>
<p>So although efficacy may be a predictor of effectiveness, we shouldn’t be disappointed if vaccines perform differently in the real world compared to their clinical trial efficacy figures.</p>
<h2>Expecting the expected</h2>
<p>Then why do pharmaceutical companies report efficacy figures when the rest of us are more interested in effectiveness?</p>
<p>The reason is because it is not always easy to define what is meant when we say vaccine effectiveness. We all want science to stop the disease and allow us to get back to normal, so this is probably what most people mean when they talk about an effective vaccine. But this apparently simple aspiration is not as straightforward as it seems.</p>
<p>Take the phrase “stopping the disease”. If we are hoping that vaccines will do this for us we may be disappointed. Vaccines can generally be useful in two different ways. They can either reduce the severity of infection, or they can stop the virus spreading between people. This latter function – <a href="https://theconversation.com/coronavirus-few-vaccines-prevent-infection-heres-why-thats-not-a-problem-152204">known as sterilising immunity</a> – is the holy grail of vaccine development, but in practice very difficult to achieve. </p>
<p>Most vaccines reduce the severity of disease and, if the vaccine designers are lucky, also reduces infectiousness at least a bit. The current coronavirus vaccines have been licensed mostly on the basis of reducing the severity of the disease simply because data on transmission is much harder to get and often requires longer studies. This is why preliminary data, like that received from Israel, is not necessarily too concerning.</p>
<p>Also consider the phrase “back to normal”. What society is really interested in is reducing the number of people admitted into hospitals, and perhaps more specifically into intensive care. Without spare capacity in hospitals, all of our lives become <a href="https://theconversation.com/we-will-not-forget-our-colleagues-who-have-died-two-doctors-on-the-frontline-of-the-second-wave-148152">significantly more dangerous</a>. </p>
<p>Taking this as the main consideration, whether vaccines prevent infectiousness by providing sterilising immunity is perhaps not what we mean by effective for getting us back to normal. Just stopping people going to hospital should be enough for the vaccine campaign to be successful.</p>
<h2>Taking the time to think</h2>
<p>All this shows that data relating to vaccine efficacy, and apparently conflicting data from real-world situations, does not represent the whole picture, especially when trying to determine national vaccination strategies. </p>
<p>Realistically, any licensed vaccine is going to be safe and have a sufficient biological effect to contribute meaningfully to getting us back to normal. On an individual level, we should take any licensed vaccine we are offered. </p>
<p>Judging which vaccine works best in which situation is a problem for professional regulators and scientists because the parameters involved are so complex that the headline figures will never reveal the true story. And this is before we even start to consider the complications caused by <a href="https://theconversation.com/coronavirus-new-variant-genomics-researcher-answers-key-questions-152381">new variants of the virus</a>.</p>
<p>We must take care when determining where new data is coming from and whether it is reliable or complete. Medical research takes a very long time because it can be quite difficult to work out what data really means. This is the reason why the scientific community has a drawn-out publication processes involving peer review. </p>
<p>This can be frustrating in a rapidly moving pandemic situation, but history (<a href="https://retractionwatch.com/retracted-coronavirus-covid-19-papers/">and even our experience over the last year or so</a>) shows that we should be very wary about making far-reaching decisions based upon <a href="https://www.open.edu/openlearn/science-maths-technology/mathematics-statistics/covid-19-making-decisions-based-on-flawed-statistics">quick and dirty interpretations of new</a> and exciting or contentious data. </p>
<p>Unfortunately the best way to catch mistakes is to spend time thinking about the research, and where possible collecting additional data to confirm or refute conclusions. This is essentially the scientific method, and operates in a very different time frame to the news or political cycle.</p><img src="https://counter.theconversation.com/content/154232/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Simon Kolstoe does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Results from individual studies are very precise, and not always the best grounds for making policy decisions.Simon Kolstoe, Senior Lecturer in Evidence-Based Healthcare and University Ethics Advisor, University of PortsmouthLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1522742021-01-27T20:47:01Z2021-01-27T20:47:01ZA universal influenza vaccine may be one step closer, bringing long-lasting protection against flu<figure><img src="https://images.theconversation.com/files/380969/original/file-20210127-13-1m5xbho.jpg?ixlib=rb-1.1.0&rect=0%2C17%2C3586%2C2640&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Wouldn't it be nice if one shot could protect you for life?</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/woman-walks-past-free-flu-shot-advertisements-outside-of-news-photo/1228109098">Bryan R. Smith/AFP via Getty Images</a></span></figcaption></figure><p>A bad year for flu can mean <a href="https://www.cdc.gov/flu/about/burden/past-seasons.html">tens of thousands</a> of deaths in the U.S. <a href="https://www.cdc.gov/flu/fluvaxview/dashboard/vaccination-dashboard.html">Getting vaccinated</a> can protect you from influenza, but you have to get the shot every year to catch up with <a href="https://doi.org/10.1038/nrmicro.2017.118">the changing virus</a> and to top up the <a href="https://www.sciencemag.org/news/2019/04/how-long-do-vaccines-last-surprising-answers-may-help-protect-people-longer">short-lived immunity the vaccine provides</a>. The vaccine’s effectiveness also depends on correct predictions about which strains will be most common in a given season. </p>
<p>For these reasons, a one-and-done universal vaccine that would provide lasting immunity over multiple flu seasons and protect against a variety of strains has been a long-term goal for scientists.</p>
<p>Researchers are now one step closer to hitting that target. Scientists recently completed the first human trial of a vaccine created by recombinant genetic technology to fool the immune system into attacking a part of the virus that does not change so fast and is common among different strains.</p>
<p>I am a microbiologist <a href="https://theconversation.com/a-massive-public-health-effort-eradicated-smallpox-but-scientists-are-still-studying-the-deadly-virus-139468">interested in infectious diseases</a>, and I’ve followed the <a href="https://theconversation.com/this-year-the-flu-came-in-two-waves-heres-why-117053">seasonal flu epidemic for several years</a>. I’m excited by this news, which could mark the turning point in the quest for a universal flu vaccine. Here’s how it all works.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/380967/original/file-20210127-13-y1yysk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="cross section of influenza virus showing RNA and surface proteins" src="https://images.theconversation.com/files/380967/original/file-20210127-13-y1yysk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/380967/original/file-20210127-13-y1yysk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/380967/original/file-20210127-13-y1yysk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/380967/original/file-20210127-13-y1yysk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/380967/original/file-20210127-13-y1yysk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/380967/original/file-20210127-13-y1yysk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/380967/original/file-20210127-13-y1yysk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">3D model of an influenza virus. Its genetic material is inside, with proteins – HA in blue, NA in red – poking out from the surface.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/computer-generated-3d-model-showing-a-cross-section-of-the-news-photo/976723030">Smith Collection/GadoArchive Photos via Getty Images</a></span>
</figcaption>
</figure>
<h2>Biology of the invading influenza virus</h2>
<p>Like the virus that causes COVID-19, the influenza virus has a protein shell that is coated by a lipid membrane. Sticking through the membrane are multiple copies of three types of proteins: haemagglutinin, abbreviated as HA; neuraminidase, abbreviated as NA; and the matrix protein, M2.</p>
<p>It’s the properties of the <a href="https://www.cdc.gov/flu/about/viruses/types.htm">HA and NA proteins</a> that distinguish the different strains of the virus. You’ve probably heard of strains like H1N1 and H3N2, both of which are <a href="https://www.cdc.gov/flu/weekly/index.htm">infecting people in the U.S. this year</a>. </p>
<p>The HA molecule is shaped a bit like a flower bud, with a stalk and a head. Once someone inhales the virus, the <a href="https://doi.org/10.1101/cshperspect.a038778">tip of the HA molecule’s head binds</a> to a receptor on the surface of the cells that line the person’s respiratory passages.</p>
<p>This initial binding is crucial as it induces the cell to engulf the virus. Once inside, the virus gets to work replicating its own genetic material. But the enzyme that copies its single-strand RNA <a href="https://doi.org/10.1128/JVI.00694-10">is very sloppy</a>; it can leave two or three mistakes, called mutations, <a href="https://doi.org/10.7554/eLife.26437">in every new copy</a>.</p>
<p>Sometimes the genetic changes are so drastic that the progeny viruses don’t survive; other times they are the start of new flu strains. Based on <a href="https://nextstrain.org/flu/seasonal/h1n1pdm/ha/2y?l=clock">viral samples collected from around the world</a>, the flu virus that arrives one year will have about seven new mutations in the gene for HA and four in the gene for NA compared to the previous year’s virus. These differences are a big part of why the same influenza vaccine won’t be as effective from one year to the next.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/380971/original/file-20210127-23-a0v88q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Immune cells fighting off flu with antibodies" src="https://images.theconversation.com/files/380971/original/file-20210127-23-a0v88q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/380971/original/file-20210127-23-a0v88q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/380971/original/file-20210127-23-a0v88q.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/380971/original/file-20210127-23-a0v88q.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/380971/original/file-20210127-23-a0v88q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=565&fit=crop&dpr=1 754w, https://images.theconversation.com/files/380971/original/file-20210127-23-a0v88q.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=565&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/380971/original/file-20210127-23-a0v88q.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=565&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Computer illustration of an immune cell (left) releasing many antibodies (white) to attack and disable invading flu particles.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/immune-response-to-a-virus-illustration-royalty-free-illustration/724237117">Juan Gaertner/Science Photo Library via Getty Images</a></span>
</figcaption>
</figure>
<h2>Fighting off a flu infection</h2>
<p>When infected with the flu virus, your immune system produces antibodies to fend it off. <a href="https://doi.org/10.3389/fimmu.2019.02997">Most of these antibodies interact with the HA head</a> and prevent the virus from getting into your cells.</p>
<p>But there’s a downside to that strong reaction. Because the immune response to the virus’s head is so vigorous, it pays little attention to <a href="https://doi.org/10.3389/fimmu.2019.02997">other parts of the virus</a>. That means that your immune system is not prepared to fend off any future infection with a virus that has a different HA head, even if the rest of the virus is identical.</p>
<p>Current flu vaccines are inactivated versions of the influenza virus and so also work by inducing antibodies targeted to the HA head. And that’s why each version of the vaccine usually works only against a particular strain. But, as the flu spreads, the rapid rate of genetic change can produce new versions of the HA head that will evade the antibodies induced by the vaccine. These newly resistant viruses will then render even the current season’s vaccine ineffective. </p>
<p>The stalk portion of the HA molecule is much more genetically stable than the head. And HA stalks from different flu strains are much more alike than their head regions are.</p>
<p>So, an obvious way to protect people against different flu strains would be to use just the HA stalk in a vaccine. Unfortunately vaccination with only a headless stalk doesn’t seem to prevent infection. </p>
<p>Scientists are currently pursuing several <a href="https://doi.org/10.3389/fimmu.2019.02997">different solutions to this problem</a>.</p>
<h2>A new kind of flu vaccine</h2>
<p>A team of scientists led by <a href="https://labs.icahn.mssm.edu/krammerlab/dr-krammer/">Florian Krammer</a> at the Icahn School of Medicine at Mount Sinai just completed the first human <a href="https://clinicaltrials.gov/ct2/show/NCT03300050">clinical trial</a> of what they hope will be a universal flu vaccine.</p>
<p>The researchers used recombinant genetic technology to create <a href="https://doi.org/10.1038/s41591-020-1118-7">flu viruses with “chimeric” HA proteins</a> – essentially a patchwork quilt built from pieces of different flu strains.</p>
<p>Volunteers for the <a href="https://doi.org/10.1038/s41591-020-1118-7">clinical trial</a> received two vaccinations separated by three months. The first dose consisted of an inactivated H1N1 virus with its original HA stalk but the head portion from a bird influenza virus. Vaccination with this virus induced a mild antibody response to the foreign head, and a robust response to the stalk. This pattern meant that the immune systems of the subjects had never encountered the head before, but had seen the stalk from previous flu vaccinations or infections.</p>
<p>The second vaccination consisted of the same H1N1 virus but with an HA head from a different bird virus. This dose elicited, again, a mild antibody response to the new head, but a further boost in response to the HA stalk. After each vaccine dose the subjects’ stalk antibody concentrations averaged about eight times higher than their initial levels.</p>
<p>Researchers found that even though the vaccine was based on the HA stalk of the H1N1 virus strain, the antibodies it elicited reacted to HA stalks from other strains too. In lab tests, the antibodies from vaccinated volunteers attacked the H2N2 virus that caused the <a href="https://www.cdc.gov/flu/pandemic-resources/1957-1958-pandemic.html">1957 Asian flu pandemic</a> and the H9N2 virus that the CDC considers to be of <a href="https://www.cdc.gov/flu/pandemic-resources/monitoring/viruses-concern.html">concern for future outbreaks</a>. The antibodies did not react to the stalk of the more distantly related H3 viral strain.</p>
<p>The antibody response also lasted a long time; after a year and a half, the volunteers still had about four times the concentration of antibodies to the HA stalk in their blood as when the trial started.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/380972/original/file-20210127-15-1cb0e0u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="surface of influenza virus with HA proteins sticking out" src="https://images.theconversation.com/files/380972/original/file-20210127-15-1cb0e0u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/380972/original/file-20210127-15-1cb0e0u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/380972/original/file-20210127-15-1cb0e0u.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/380972/original/file-20210127-15-1cb0e0u.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/380972/original/file-20210127-15-1cb0e0u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/380972/original/file-20210127-15-1cb0e0u.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/380972/original/file-20210127-15-1cb0e0u.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Avoiding the vigorous immune response to the protein’s head means the immune cells can concentrate on the more stable stalk of the protein.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/flu-virus-illustration-royalty-free-illustration/713781829">Kateryna Kon/Science Photo Library via Getty Images</a></span>
</figcaption>
</figure>
<p>Since this was a <a href="https://theconversation.com/from-the-research-lab-to-your-doctors-office-heres-what-happens-in-phase-1-2-3-drug-trials-138197">phase 1 clinical trial</a> testing only for adverse effects (which were minimal), the researchers didn’t expose vaccinated people to the flu to test if their new antibodies protected them.</p>
<p>However, they did inject the subjects’ blood serum, which contains the antibodies, into mice to see if it would protect them against the flu virus. Getting a shot of serum taken from volunteers a month after receiving the booster shot, when antibody levels were high, led to mice being 95% healthier after virus exposure than mice who got blood serum from nonvaccinated volunteers. Even the mice who received serum that was collected from vaccinated volunteers a year after the start of the trial were about 30% less sick.</p>
<p><a href="https://doi.org/10.1038/s41591-020-1118-7">These results</a> show that vaccination with a chimeric flu protein can provide long-lasting immunity to several different strains of the influenza virus. Scientists will need to <a href="https://doi.org/10.1093/infdis/jiy103">continue optimizing this approach</a> so it works for different types and strains of influenza. But the success of this first human trial means you may one day get a single shot and, at last, be free from the flu.</p>
<p>[<em>The Conversation’s science, health and technology editors pick their favorite stories.</em> <a href="https://theconversation.com/us/newsletters/science-editors-picks-71/?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=science-favorite">Weekly on Wednesdays</a>.]</p><img src="https://counter.theconversation.com/content/152274/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Patricia L. Foster is affiliated with the Union of Concerned Scientists and Concerned Scientists at Indiana University. </span></em></p>You need a new shot every year because current flu vaccines provide limited and temporary protection. But researchers’ new strategy could mean a one-and-done influenza vaccine is on the way.Patricia L. Foster, Professor Emerita of Biology, Indiana UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1509672020-12-01T15:22:05Z2020-12-01T15:22:05ZCOVID-19 vaccine trials in Africa: what’s promising, and what’s problematic<figure><img src="https://images.theconversation.com/files/371752/original/file-20201127-19-7ifqee.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>Scientists are working around the clock to develop and test vaccines against SARS-CoV-2, the causative agent of COVID-19. Experts agree that widespread use of safe and effective vaccines will rapidly contain <a href="https://www.nationalgeographic.com/science/2020/04/why-coronavirus-vaccine-could-take-way-longer-than-a-year/">the COVID-19 pandemic</a>, preventing transmission and disease. </p>
<p>A key step in the process of any vaccine development is clinical testing, which involves assigning a vaccine or a placebo to human subjects, then evaluating the health effects over a period of time. This testing helps to demonstrate safety in diverse human populations living in different settings, and to determine vaccine efficacy – the ability to prevent infection and disease.</p>
<p>Globally, COVID-19 vaccine <a href="https://www.who.int/news/item/24-08-2020-172-countries-and-multiple-candidate-vaccines-engaged-in-covid-19-vaccine-global-access-facility">trials</a> are being conducted in all continents, representing all diverse human populations in the world. In Africa, <a href="https://www.arabnews.com/node/1744091/middle-east">Egypt</a> and <a href="https://theconversation.com/pasha-79-why-south-africas-role-in-covid-19-vaccine-trials-is-important-145472">South Africa</a> are participating in these trials. Many other countries are also preparing to participate.</p>
<p>To date there are 260 COVID-19 vaccine candidates at different stages of development. Sixty of these are undergoing clinical testing (human trials) in different phases. This includes phase III trials – the point at which scientists aim to determine how well a vaccine protects (efficacy) trial participants from infection or severe COVID-19 symptoms. </p>
<p>November 2020 has been a celebratory month. Preliminary phase III data of three different COVID-19 vaccine candidates showed impressively high efficacy ranging from 70% to 95%. All three – <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-announce-vaccine-candidate-against">Pfizer/BioNTech</a>, <a href="https://www.modernatx.com/modernas-work-potential-vaccine-against-covid-19">Moderna mRNA-1273</a> and <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31604-4/fulltext">Oxford ChAdOx1-S</a> vaccines – are in the late stage of phase III clinical trials. Pfizer/BioNTech and Oxford ChAdOx1-S are being tested in Africa too. After investigations of an initial safety concern in phase III trial, the Oxford ChAdOx1-S vaccine testing <a href="https://www.bmj.com/content/370/bmj.m3525">has proceeded well</a>.</p>
<p>The groundbreaking developments offer hope and optimism. But there are still major obstacles ahead, particularly for developing countries. Chief among these are the fact that at least one of the vaccines showing promise needs to be kept at extremely low temperatures prior to use. This will be a difficult ask for most African countries.</p>
<p>In addition, there are concerns about access to the vaccines once manufacturing starts. Among the key concerns is the availability of sufficient vaccine doses to meet the high demand. And then there’s the question of affordability. Resources will be urgently needed to procure and distribute COVID-19 vaccines at a rapid pace. </p>
<p>A great deal of focus is being placed on the <a href="https://www.gavi.org/covax-facility">COVAX Facility, a GAVI co-led</a> global risk sharing plan. This is overseeing the pooling of procurement and equitable distribution of eventual COVID-19 vaccines.</p>
<h2>The promise</h2>
<p>There are three vaccines at phase III stage with a similar choice of an antigen – the SARS-CoV-2 spike protein. But they work differently in the way they teach the immune system to protect our bodies from COVID-19.</p>
<p>Pfizer/BioNTech is a mRNA vaccine. Such vaccines work by instructing the human cells to make a small part of the virus surface protein and induce the appropriate type of immune response that is thought to confer protection. In this case, it is an immune response to the SARS-CoV-2 spike protein. This protein plays a key role in enabling coronaviruses to infect human cells and replicate. </p>
<p>In some infected people, COVID-19 disease develops, whereas others remain asymptomatic, without any signs or symptoms of the disease. Preliminary data show no major safety concerns are associated with a two-dose administration of the vaccine. This mRNA-based COVID-19 vaccine induces T-cell and strong neutralising antibody immune responses. Both T-cell and antibody immune responses are thought to be critical in protecting against COVID-19. A similar mRNA vaccine, made by Moderna, has shown comparable results.</p>
<p>Efficacy of 95% has been reported for the Pfizer/BioNTech (mRNA) vaccine, far exceeding the expectations. This type of vaccine can be rapidly manufactured and scaled to capacity to meet the high demand for millions of doses. If licensed, it will be the first mRNA vaccine approved for human use by the regulatory authorities. </p>
<p>Oxford ChAdOx1-S is a non-replicating viral vector vaccine. The viral vector, or backbone, used in this vaccine is based on the chimpanzee adenovirus (ChAd). The choice of this type of vector is to circumvent common pre-existing immunity to human adenoviruses (HAdV) that would blunt the ability of such a vaccine to engage the human immune system. </p>
<p>Already, scientists have experience with clinical testing (safety and immunological profiles) of the ChAd <a href="https://academic.oup.com/cid/article/70/10/2073/5537685">viral vectored vaccines</a>.</p>
<p>The Oxford ChAdOx1-S works by using a replication-deficient adenovirus vector to conveniently deliver the spike protein to immune cells or tissues, thereby inducing the desired immune response against SARS-CoV-2. The vaccine-induced immunity comprises of T-cell and strong neutralising (infection-blocking) antibody immune responses. </p>
<p>Novavax NVX-CoV2373 is a protein subunit vaccine. Subunit vaccines work by presenting a specific antigen that stimulates the immune system to mount a response. Importantly, these types of vaccines require combination with adjuvants (a compound that enhances an immune response), as the antigens alone are not enough to induce optimal and long-term immunity. </p>
<p>The antigen (spike protein) in NVX-CoV2373 vaccine is made and purified from cell culture, then formulated – along with Novavax’s saponin-based Matrix-M adjuvant – to a nanoparticle. There is vast clinical experience of this type of vaccine platform in terms of safety and immunogenicity, such as the seasonal influenza vaccine. </p>
<p>Preliminary data shows NVX-CoV2373 vaccine-induced immunity comprises T-cell and strong neutralising antibody immune responses. It is likely this two-dose schedule vaccine candidate will show high efficacy. </p>
<h2>The problems</h2>
<p>A big challenge for the Pfizer/BioNTec vaccine is the cold chain requirements. It needs to be transported and stored at unusually low temperatures (-70°C, on dry ice) prior to use. Immunisation programmes – particularly those on the continent – don’t have the vaccine supply and cold chain infrastructures that can optimally handle this vaccine. This is especially true at the level-one healthcare facilities where immunisations routinely take place. </p>
<p>This means that significant investments will have to be made prior to rollout to communities in remote areas. This could cause massive delays in the use of the vaccine, especially in low- and middle-income countries. The good news is that innovative approaches, such as design and development of appropriate transport containers, <a href="https://www.mecotec.net/en/first-mobile-hybrid-container-solution-for-covid-19-vaccines/">may address these challenges</a>. </p>
<p>The other two vaccines can be handled within the current immunisation cold chain infrastructure that keeps temperature at a range of 2°C to 8°C prior to use.</p>
<p>Another potential challenge is that the use of any of these vaccines by national immunisation programmes will need to be informed by high quality and timely evidence that takes local context into consideration. This means national policy makers must urgently and meticulously consider the merits and demerits of each of the vaccines prior to deciding which one to use.</p>
<p>On cost and access, a great deal of effort is being put into the COVAX Facility. This seems to be Africa’s only insurance policy against being the last in the queue.</p><img src="https://counter.theconversation.com/content/150967/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Benjamin Kagina receives funding from the Wellcome Trust and from Bill and Melinda Gates Foundation. Benjamin has also received educational grants from Sanofi Pasteur, Pfizer, GSK and Merck.</span></em></p>There are three promising COVID-19 trials.Benjamin Kagina, Senior Research Officer, Vaccines For Africa Initiative, Faculty of Health Sciences, University of Cape TownLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1507862020-11-29T09:17:37Z2020-11-29T09:17:37ZBattles won – and lost – against AIDS hold valuable lessons for managing COVID-19<figure><img src="https://images.theconversation.com/files/371251/original/file-20201125-13-65tf7u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source"> Sonali Pal Chaudhury/NurPhoto via Getty Images</span></span></figcaption></figure><p>World AIDS Day this year finds us still deep amid another pandemic – <a href="https://theconversation.com/africa/covid-19">COVID-19</a>. </p>
<p>The highly infectious novel coronavirus has swept across the world, devastating health systems and laying waste to economies as governments introduced drastic measures to contain the spread. Not since the HIV/AIDS pandemic of the 1990s have countries faced such a common health threat.</p>
<p>This explains why UNAIDS has selected the theme “<a href="https://www.unaids.org/en/World_AIDS_Day">Global Solidarity, Shared Responsibility</a>” for this year’s World AIDS Day. </p>
<p>Infectious diseases such as these remain a major threat to human health and prosperity. Around <a href="https://www.unaids.org/sites/default/files/media_asset/UNAIDS_FactSheet_en.pdf">32.7 million people</a> have died from AIDS-related illnesses in the last 40 years. At the time of writing, <a href="https://coronavirus.jhu.edu/map.html">1.4 million people</a> had already died from COVID-19 in just one year. </p>
<p>These diseases take incredible expertise, collaboration and dedication from all levels of society to track, understand, treat and prevent.</p>
<p>The HIV/AIDS response played out over a much longer trajectory than COVID-19. But it is, in some respects, a shining example of what can be achieved when countries and people work together. The work of organisations such as the <a href="https://www.who.int/">World Health Organisation</a>, <a href="https://www.unaids.org/en">UNAIDS</a> and the <a href="https://www.iasociety.org/">International AIDS Society</a> help to coordinate rapid sharing of information and resources between healthcare providers and communities. </p>
<p>The <a href="https://www.theglobalfund.org/en/">Global Fund</a> and <a href="https://www.state.gov/pepfar/">PEPFAR</a> have mobilised resources that have helped to reduce morbidity and mortality in low- and middle-income regions. AIDS-related deaths have declined worldwide by <a href="https://www.unaids.org/sites/default/files/media_asset/UNAIDS_FactSheet_en.pdf">39% since 2010</a>. </p>
<p>These and other groups have also fought against high drug prices that would render medication inaccessible to many in the developing world. In South Africa, the epicentre of the HIV epidemic, a day’s supply of the simplest antiretrovirals <a href="https://www.internationalbudget.org/wp-content/uploads/AIDS-in-South-Africa-Report-on-Intergovernmental-Funding-Flows-for-Integrated-Response-in-the-Social-Sector.pdf">cost about R250 in 2002</a>. Today easier, more palatable treatment taken once per day <a href="https://www.spotlightnsp.co.za/2019/02/26/analysis-how-a-cutting-edge-medicine-made-it-to-sas-new-arv-tender/">costs</a> a few rands. </p>
<p>Collaboration and co-ordination has also meant that medications have been developed and tested in populations across the world. And once available, global guidelines and training opportunities ensure that healthcare provision and quality is standardised. </p>
<p>Many of these achievements did not come without a fight. Dedicated and sustained activism, at a political and community level were required to drive down drug pricing for the global South and is constantly required to ensure inclusive distribution of resources.</p>
<p>The corollary is also true – areas where the world continues to struggle arise predominantly where there’s a lack of solidarity and agreement. These include a lack of political support to implement evidence-based protection mechanisms for vulnerable or stigmatised populations. For example the legalisation of homosexuality. This results in continued but avoidable HIV infection and related mortality. </p>
<p>These lessons need to be taken on board as the world prepares for the next phase of managing COVID-19. All the interventions that helped contain and manage HIV and AIDS are critical in ensuring that no country, regardless of developmental status, and no population, especially those that face stigma and battle to access healthcare services, are left behind.</p>
<h2>Building on existing systems</h2>
<p>The lessons learnt from HIV and AIDS can be used to inform the COVID-19 response as the challenges are similar. </p>
<p>Many of the ongoing COVID-19 vaccine trials are taking place in multiple countries, including South Africa. The capacity to conduct these studies, including the clinical staff and trial sites, are well established as a result of decades of HIV/AIDS research. There are fears that developing nations might be excluded from accessing an effective COVID-19 vaccine. But global mechanisms are now in place to avoid this and to, instead, encourage and enable global solidarity, some of which were championed by the HIV/AIDS response. </p>
<p>The <a href="https://www.who.int/initiatives/act-accelerator">Access to COVID-9 Tools (ACT)-Accelerator,</a> established by the World Health Organisation in April 2020 in collaboration with many other global organisations, governments, civil society and industry, have committed through the pillar known as Covax, to equitable distribution of a COVID-19 vaccine as well as diagnostic tests and treatments. These global institutions and mechanisms require continued support.</p>
<p>With the deployment of an effective vaccine, an end to COVID-19 might soon be in sight. For HIV, vaccine development has been more complex and disappointing. The global community needs to remain committed to promoting access and support for the many incredible prevention and treatment options that are available. The unprecedented effort on the part of private industry in the COVID-19 vaccine response shines a light on what can be achieved when all interested parties engage. The HIV and TB vaccine endeavours need a similar effort.</p>
<p>These are not the only pandemics the world will face. In fact, there are strong predictions that the emergence of new pandemics will increase in the future. This is due to the effects of globalisation, climate change and proximity to wildlife. </p>
<p>The best hope for humanity is to not lose sight of what these pandemics cost us in terms of loved ones, in terms of freedom and economically. We must prepare now collectively across countries and across all levels of society. These preparations need to be grounded in the lessons learnt from HIV/AIDS and re-learnt from COVID-19. </p>
<h2>Social solidarity</h2>
<p>The success of the global response to current and emerging pandemics will rely on the ability of the less vulnerable to acknowledge their shared responsibility and respond to those calls.</p>
<p>An important truth of the HIV epidemic is that it doesn’t discriminate. No infectious disease acknowledges political borders and everybody is at risk of being infected or affected. If nothing else, because of this we need to continue to work together on a global scale knowing that “no one is safe, until everyone is safe”.</p>
<p><em>Carey Pike, Executive Research Assistant at the Desmond Tutu Health Foundation contributed to this article.</em></p><img src="https://counter.theconversation.com/content/150786/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Linda-Gail Bekker receives funding from the National Institutes of Health, USA and other similar research funding agencies. </span></em></p>The HIV/AIDS response played out over a much longer trajectory than COVID-19. But it is, in some respects, a shining example of what can be achieved when countries and people work together.Linda-Gail Bekker, Professor of medicine and deputy director of the Desmond Tutu HIV Centre at the Institute of Infectious Disease and Molecular Medicine, University of Cape TownLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1504432020-11-19T07:37:34Z2020-11-19T07:37:34Z‘Very convincing evidence’: Pfizer now has the data it needs to apply for COVID vaccine approval<figure><img src="https://images.theconversation.com/files/370247/original/file-20201119-19-1p7t20q.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C6000%2C3988&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>On Wednesday, Pfizer and BioNTech announced their mRNA vaccine has demonstrated a remarkable <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-conclude-phase-3-study-covid-19-vaccine">95% efficacy</a> in the “final efficacy analysis” of its phase 3 trial. </p>
<p>The news comes hot on the heels of Pfizer/BioNTech’s <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-announce-vaccine-candidate-against">interim analysis</a> last week, which pointed to greater than 90% efficacy, and <a href="https://investors.modernatx.com/news-releases/news-release-details/modernas-covid-19-vaccine-candidate-meets-its-primary-efficacy">Moderna’s announcement</a> on Monday, also based on an interim analysis, that its vaccine is 94.5% efficacious. </p>
<p>The word “<a href="https://theconversation.com/how-to-read-results-from-covid-vaccine-trials-like-a-pro-149916">efficacy</a>” describes how well the vaccine offers protection against the target disease during the trial, whereas the word “effectiveness” refers to how well the vaccine protects against the disease in the real world.</p>
<p>This “final efficacy analysis” represents the Pfizer/BioNTech study’s “primary endpoint” — which means there are enough volunteers in the study who have developed COVID-19 to perform a solid evaluation of whether the vaccine is working. </p>
<p>Before the study began, statisticians designing the study identified that <a href="https://pfe-pfizercom-d8-prod.s3.amazonaws.com/2020-11/C4591001_Clinical_Protocol_Nov2020.pdf">164 people with confirmed COVID-19</a> would be enough cases to evaluate efficacy (more than 43,000 participants are enrolled in the trial in total). </p>
<p>There were 94 people who had COVID-19 in the <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-announce-vaccine-candidate-against">interim analysis last week</a>, and they reached <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-conclude-phase-3-study-covid-19-vaccine">170 people this week</a> — 162 of whom got the placebo and only eight of whom received the vaccine. This is very convincing evidence that this vaccine protects against developing COVID-19 disease.</p>
<p>The fact the primary endpoint was reached so quickly indicates <a href="https://covid.cdc.gov/covid-data-tracker/#cases_casesper100klast7days">cases are surging in the United States</a> across a lot of the sites where the trial is taking place. Yes, these surging cases are providing more data than anticipated for phase 3 clinical studies; but they also highlight the urgency of the situation in the US.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/90-efficacy-for-pfizers-covid-19-mrna-vaccine-is-striking-but-we-need-to-wait-for-the-full-data-149818">90% efficacy for Pfizer's COVID-19 mRNA vaccine is striking. But we need to wait for the full data</a>
</strong>
</em>
</p>
<hr>
<h2>Deeper insights</h2>
<p>Pfizer/BioNTech have provided three additional important pieces of information. </p>
<p>First, the vaccine appears to be safe. Volunteers in the study were asked to report different symptoms after receiving the vaccine, and the most common symptoms of note were <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-conclude-phase-3-study-covid-19-vaccine">fatigue and headaches</a> (3.8% of participants experienced more severe fatigue, and 2% headaches).</p>
<p>Second, the vaccine appears to protect against severe disease. The trial saw ten people become severely unwell with COVID-19, <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-conclude-phase-3-study-covid-19-vaccine">only one of whom had received the vaccine</a>. This is a huge relief, because severe COVID-19 puts immense pressure on health-care systems.</p>
<p>Third, they’ve reported the vaccine has 94% efficacy in older people. This is crucial as older adults are bearing the brunt of COVID-19. In Australia, people over 65 make up only <a href="http://www9.health.gov.au/cda/source/rpt_5.cfm">20% of cases</a> but <a href="https://www.mja.com.au/journal/2020/outcomes-covid-19-patients-admitted-australian-intensive-care-units-during-early-phase">almost 50% of all ICU admissions</a> and <a href="https://www.covid19data.com.au">more than 95% of deaths</a> from COVID-19. </p>
<p>This efficacy in older people exceeds what many researchers had anticipated, as vaccines <a href="https://academic.oup.com/cid/article/55/7/951/427559">often don’t work as well</a> in this group. </p>
<figure class="align-center ">
<img alt="An elderly lady wearing a mask walks with a frame in a garden." src="https://images.theconversation.com/files/370250/original/file-20201119-15-s607a3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/370250/original/file-20201119-15-s607a3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/370250/original/file-20201119-15-s607a3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/370250/original/file-20201119-15-s607a3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/370250/original/file-20201119-15-s607a3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/370250/original/file-20201119-15-s607a3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/370250/original/file-20201119-15-s607a3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The Pfizer/BioNTech vaccine appears to work equally well in older people.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<h2>It’s not a competition</h2>
<p>The Moderna vaccine has also shown <a href="https://investors.modernatx.com/news-releases/news-release-details/modernas-covid-19-vaccine-candidate-meets-its-primary-efficacy">promising results</a> on those first two measures — safety and protecting against severe disease. We await data on its efficacy in older people.</p>
<p>This rapid-fire succession of press releases may feel like Pfizer/BioNTech and Moderna are competing for the “biggest” efficacy, but competition is not the driving factor.</p>
<p>The primary endpoints are pre-defined by both companies and, when the study reaches them, an interim or final analysis can be performed. Data and safety monitoring boards, independent from the companies, perform these analyses.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/modernas-covid-vaccine-reports-95-efficacy-it-means-we-might-have-multiple-successful-vaccines-150266">Moderna's COVID vaccine reports 95% efficacy. It means we might have multiple successful vaccines</a>
</strong>
</em>
</p>
<hr>
<p>From a scientific perspective, it’s plausible these two vaccines would have similar efficacy, because they use very similar mRNA vaccine designs. In fact, it’s reassuring they are similar because, in science, we must be able to repeat our results. This gives us confidence the data are correct and that we’ll see similar results outside the lab.</p>
<p>In any scenario, competition is redundant when you consider the size of the problem. Nearly eight billion people around the world urgently need a vaccine. <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-conclude-phase-3-study-covid-19-vaccine">Pfizer/BioNTech</a> and <a href="https://investors.modernatx.com/news-releases/news-release-details/modernas-covid-19-vaccine-candidate-meets-its-primary-efficacy">Moderna</a> have each indicated they can make enough vaccines for around 500 million people next year. That still leaves seven billion people needing a vaccine — more than enough of a market for both companies, and more.</p>
<p>Any way you look at it, the real competition is against the virus.</p>
<h2>What’s next?</h2>
<p>In <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-conclude-phase-3-study-covid-19-vaccine">the coming days</a>, Pfizer/BioNTech will apply to the US Food and Drug Administration (FDA) for an emergency use approval for their vaccine. Moderna and other vaccine developers likely won’t be far behind once they reach their primary endpoints. </p>
<p>Applications to other regulatory bodies around the world will follow, including the Therapeutic Goods Administration in Australia. A successful emergency use approval with the FDA can accelerate approvals with other bodies.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/how-to-read-results-from-covid-vaccine-trials-like-a-pro-149916">How to read results from COVID vaccine trials like a pro</a>
</strong>
</em>
</p>
<hr>
<p>This study will <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-conclude-phase-3-study-covid-19-vaccine">continue for two years</a> to collect “secondary endpoints” — more in-depth details on how the vaccine works and its safety longer term. It will aim to answer three important questions:</p>
<ul>
<li><p><strong>longevity:</strong> how long the vaccine protects people for</p></li>
<li><p><strong>infection:</strong> these latest results show that the vaccine prevents people from getting sick and showing symptoms of COVID-19. But we also need to see whether the vaccine protects people from getting infected in the first place</p></li>
<li><p><strong>transmission:</strong> whether the vaccine reduces the likelihood of an infected but vaccinated person passing the virus on to another person.</p></li>
</ul>
<p>It’s fairly straightforward to measure whether a vaccine prevents people from developing disease — you wait for people to report symptoms that could be COVID-19 and then perform a COVID test. Longer timelines and more complicated, laborious lab work are needed to learn about longevity, infection and transmission. </p>
<p>So, there are more insights into the virus and vaccines to come. But these studies are an exciting landmark in vaccine development.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/why-we-should-prioritise-older-people-when-we-get-a-covid-vaccine-148432">Why we should prioritise older people when we get a COVID vaccine</a>
</strong>
</em>
</p>
<hr>
<img src="https://counter.theconversation.com/content/150443/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Kylie Quinn is affiliated with RMIT University and is a member of the Vaccine Alliance Aotearoa New Zealand Advisory Group. She receives funding from the Rebecca L. Cooper Foundation.</span></em></p>Pfizer and BioNTech have announced 95% efficacy for their mRNA vaccine, having met the final target they need to before seeking regulatory approval.Kylie Quinn, Vice-Chancellor's Research Fellow, School of Health and Biomedical Sciences, RMIT UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1499572020-11-18T19:56:01Z2020-11-18T19:56:01ZCOVID-19 vaccines: How Pfizer’s and Moderna’s 95% effective mRNA shots work<figure><img src="https://images.theconversation.com/files/369749/original/file-20201117-23-1x7lt37.jpg?ixlib=rb-1.1.0&rect=0%2C36%2C7445%2C5456&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A volunteer gets an injection of Moderna’s possible COVID-19 vaccine on July 27, 2020. Moderna announced Nov. 16 that its vaccine is proving highly effective in a major trial.</span> <span class="attribution"><span class="source">(AP Photo/Hans Pennink)</span></span></figcaption></figure><p>The COVID-19 pandemic has driven a massive allocation of resources towards producing solutions, from <a href="https://dx.doi.org/10.1016%2Fj.virusres.2020.198137">identifying life-saving medications</a>, tracking <a href="https://doi.org/10.1101/2020.08.23.20178236">how the virus spreads</a> and ultimately to preventing infection with vaccines. </p>
<p>As a physician scientist, I study how the virus has evolved over the pandemic, since any changes in the virus could also change the effectiveness of current treatments. On Nov. 9, Pfizer announced preliminary trial results showing that a vaccine it developed with BioNTech was about <a href="https://www.nature.com/articles/d41586-020-03166-8">90 per cent effective</a>. That was followed up nine days later with <a href="https://www.reuters.com/article/us-health-coronavirus-vaccines-pfizer/a-special-day-end-of-pfizer-trial-paves-way-for-a-covid-shot-this-year-idUSKBN27Y1GM">final trial results</a> and two months of safety data, indicating a 95 per cent effectiveness rate. </p>
<p>Pfizer announced on Nov. 18 that it intends to file for emergency authorization with the U.S. Food and Drug Administration.</p>
<p>Meanwhile, on Nov. 16, <a href="https://www.reuters.com/article/health-coronavirus-vaccines-moderna-int/moderna-trial-success-gives-world-more-hope-in-race-to-end-pandemic-idUSKBN27W1EJ">Moderna announced preliminary results</a> for its own vaccine, developed with the U.S. National Institutes of Health, which also indicated effectiveness of about 95 per cent. </p>
<p>This is good news, but we need to understand what it means so life can ultimately go back to normal.</p>
<h2>DNA, messenger RNA and proteins</h2>
<p>Both Pfizer’s and Moderna’s vaccines are mRNA-based. In each of our cells, DNA produces messenger RNA (mRNA) containing the templates for making proteins. It’s called messenger RNA because it carries that information to other parts of the cell, where the instructions are read and followed to produce specific proteins. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/369754/original/file-20201117-21-6pxdt8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A multicoloured, triangular protein with a bumpy surface against a black background." src="https://images.theconversation.com/files/369754/original/file-20201117-21-6pxdt8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/369754/original/file-20201117-21-6pxdt8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/369754/original/file-20201117-21-6pxdt8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/369754/original/file-20201117-21-6pxdt8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/369754/original/file-20201117-21-6pxdt8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/369754/original/file-20201117-21-6pxdt8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/369754/original/file-20201117-21-6pxdt8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">3D print of the spike protein of SARS-CoV-2, the virus that causes COVID-19. Spike proteins cover the surface of the virus and enable it to enter and infect human cells.</span>
<span class="attribution"><span class="source">(NIH)</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>When a patient is injected with mRNA in a vaccine, their cells use the information in that mRNA to create a protein: in this case, a version of the spike protein from the coronavirus that causes COVID-19. The immune system recognizes that protein as a signal to produce antibodies and immune cells. </p>
<p>An <a href="https://dx.doi.org/10.1038%2Fnrd.2017.243">mRNA vaccine has some advantages for mass vaccination</a>. It can produce robust immunity, can be made rapidly at low cost, and, like <a href="https://theconversation.com/covid-19-vaccine-update-pfizer-may-be-the-frontrunner-but-canada-has-hedged-its-bets-149962">inactivated and subunit vaccines</a>, it is impossible for it to cause someone to develop the illness. </p>
<h2>Building immunity</h2>
<p>This vaccine has the potential to protect many people from this devastating virus. When it is said that a vaccine is 90 per cent effective, this means that if 100 people received the vaccine and were then exposed to the virus, 90 would be unlikely to get sick. While 10 would be at risk of still developing the infection, fortunately protection from vaccines is not all-or-nothing. These 10 individuals could have milder disease than someone who did not receive the vaccine. </p>
<figure class="align-center ">
<img alt="People wearing face masks walk past a Pfizer sign at street level." src="https://images.theconversation.com/files/369753/original/file-20201117-17-109yty1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/369753/original/file-20201117-17-109yty1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/369753/original/file-20201117-17-109yty1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/369753/original/file-20201117-17-109yty1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/369753/original/file-20201117-17-109yty1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/369753/original/file-20201117-17-109yty1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/369753/original/file-20201117-17-109yty1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Pedestrians walk past Pfizer world headquarters in New York on Nov. 9, 2020.</span>
<span class="attribution"><span class="source">(AP Photo/Bebeto Matthews)</span></span>
</figcaption>
</figure>
<p>It takes time for immune systems to prepare to fight infections. Think of building immunity to SARS-CoV-2, the virus that causes COVID-19, like preparing to run a marathon. First, the runner must register, just as the immune system must be exposed to the infectious agent. Then, they need to build stamina. For the immune system, this means making antibodies and immune cells. Finally, they run the marathon: the bolstered immune system now removes the infectious agent from the body, or prevents it from doing further damage.</p>
<p>In both the <a href="https://www.clinicaltrials.gov/ct2/show/study/NCT04368728">Pfizer</a> and <a href="https://www.clinicaltrials.gov/ct2/show/NCT04470427">Moderna clinical trials</a>, subjects received the vaccine in two doses, three or four weeks apart, respectively. That’s about how much time it takes for the stimulated immune system to produce meaningful protection. A booster vaccine was given to produce even more antibodies and immune cells. In terms of the marathon example, this is like doing a practice marathon around three weeks into training. The runner will do better than they would have on day one, but more training is likely still needed. The booster vaccine provides that extra training.</p>
<h2>The beginning of the end</h2>
<p>Should we expect the pandemic to be over once a vaccine is available for public use? Not exactly. A vaccine will not be perfect, and it takes time for the immune system to be ready to protect us.</p>
<figure class="align-center ">
<img alt="A man in a face mask walks in front of the entrance to a white building, under the name Moderna in red letters." src="https://images.theconversation.com/files/369752/original/file-20201117-15-tldxqj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/369752/original/file-20201117-15-tldxqj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/369752/original/file-20201117-15-tldxqj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/369752/original/file-20201117-15-tldxqj.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/369752/original/file-20201117-15-tldxqj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/369752/original/file-20201117-15-tldxqj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/369752/original/file-20201117-15-tldxqj.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A man stands outside an entrance to a Moderna building in Cambridge, Mass., on May 18, 2020.</span>
<span class="attribution"><span class="source">(AP Photo/Bill Sikes)</span></span>
</figcaption>
</figure>
<p>In addition, it is possible that the vaccines will be less effective than cited. Clinical trials are carefully set up, but it is possible that the virus will have evolved enough since the vaccines were designed so they will provide less benefit. It will also take time for enough vaccine to be made and administered for the population to achieve <a href="https://www.who.int/news-room/q-a-detail/herd-immunity-lockdowns-and-covid-19">herd immunity</a>. </p>
<p>Masks and social distancing will still most likely be necessary throughout 2021 because it takes time to accomplish such large-scale projects. We cannot expect <a href="https://theconversation.com/5-failings-of-the-great-barrington-declarations-dangerous-plan-for-covid-19-natural-herd-immunity-148975">herd immunity from our neighbours getting sick</a> to get the world back to normal, even while neighbours are receiving vaccines. The human cost is unacceptable and the virus is too infectious for this to produce meaningful results unless <a href="https://doi.org/10.1016/j.immuni.2020.04.012">67 per cent of the population is infected</a>, with a lot of people dying up to that point and afterwards.</p>
<p>We are in a scary time but have reason to have hope. The news of the Pfizer and Moderna vaccines is good news and could potentially bring the world back to something more normal. We must not forget that it will take time and all of us working together. Masks and social distancing are our reality right now, and will remain so until at least next year. We must persevere with these measures, even when we find them frustrating. There is a light at the end of the tunnel and we can all reach it if we work together.</p><img src="https://counter.theconversation.com/content/149957/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Julian Daniel Sunday Willett does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Two pharma companies have announced early COVID-19 vaccine trial results with over 90 per cent effectiveness. What does that mean for getting back to normal?Julian Daniel Sunday Willett, PhD Student, Quantitative Life Sciences, McGill UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1495222020-11-05T05:56:22Z2020-11-05T05:56:22ZWhat do we know about the Novavax and Pfizer COVID vaccines that Australia just signed up for?<figure><img src="https://images.theconversation.com/files/367599/original/file-20201104-23-1xy5a9j.jpg?ixlib=rb-1.1.0&rect=1%2C1%2C1024%2C530&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-vector/development-creation-covid19-vaccine-design-by-1782359774">Shutterstock</a></span></figcaption></figure><p>The federal government’s <a href="https://www.abc.net.au/news/2020-11-04/two-new-coronavirus-vaccine-deals-50-million-doses-government/12849572">announcement</a> of agreements to supply vaccines from Novavax and Pfizer/BioNTech <a href="https://www.pm.gov.au/media/australia-secures-further-50-million-doses-covid-19-vaccine">potentially increases</a> the pool of COVID-19 vaccines Australians will be able to access.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1324101696289648641"}"></div></p>
<p>These two vaccines are in addition to supply arrangements for vaccines from Oxford University/AstraZeneca and the University of Queensland/CSL, <a href="https://theconversation.com/putting-our-money-on-two-covid-vaccines-is-better-than-one-why-australias-latest-vaccine-deal-makes-sense-145693">announced in September</a>. Australia will also have access to vaccines via the World Health Organisation-backed <a href="https://theconversation.com/australias-just-signed-up-for-a-shot-at-9-covid-19-vaccines-heres-what-to-expect-146750">COVAX initiative</a>.</p>
<p>However, these arrangements depend on whether the vaccines are shown to be safe and effective in clinical trials, which are still ongoing. So what do we know about the two vaccines in this latest deal?</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/scott-morrison-to-announce-two-new-covid-vaccine-deals-149458">Scott Morrison to announce two new COVID vaccine deals</a>
</strong>
</em>
</p>
<hr>
<h2>What do we know about the Novavax vaccine?</h2>
<p>The Novavax vaccine, NVX-CoV2373, contains <a href="https://ir.novavax.com/news-releases/news-release-details/novavax-present-covid-19-vaccine-data-world-vaccine-congress">purified pieces</a> of the spike protein of SARS-CoV-2, the virus that causes COVID-19. </p>
<p>These proteins are administered with an adjuvant, a molecule that enhances the immune response. The idea is that when this vaccine is administered, the body recognises its contents as “foreign” and mounts a protective immune response.</p>
<p>Early clinical trials were performed <a href="https://www.nejm.org/doi/10.1056/NEJMoa2026920?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed">in Australia</a>. In the phase 1 clinical trials, the vaccine was generally well-tolerated and produced <a href="https://www.nejm.org/doi/10.1056/NEJMoa2026920?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed">strong antibody responses</a>, stronger than what we see in patients recovering from COVID-19.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/from-adenoviruses-to-rna-the-pros-and-cons-of-different-covid-vaccine-technologies-145454">From adenoviruses to RNA: the pros and cons of different COVID vaccine technologies</a>
</strong>
</em>
</p>
<hr>
<p>In September, Novavax launched a phase 3 clinical trial <a href="https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-004123-16/GB">in the United Kingdom</a>. Further large-scale clinical trials are planned for other countries in late 2020 and early 2021. </p>
<p>If the Novavax vaccine is successful <a href="https://www.health.gov.au/resources/publications/coronavirus-covid-19-information-about-the-novavax-vaccine-for-covid-19">40 million doses</a> are expected to be available in Australia during 2021, with the option to buy a further 10 million. </p>
<h2>What do we know about the Pfizer vaccine?</h2>
<p>The vaccine developed by Pfizer, BNT162b2, is based on the genetic material mRNA (or messenger ribonucleic acid). Such mRNA vaccines carry a piece of genetic material that codes for viral proteins, or parts of them. Once inside your cells, the mRNA instructs your cells’ protein factories to make copies of these viral proteins. These then stimulate your immune system to mount a protective immune response.</p>
<p>Pfizer’s BNT162b2 vaccine <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-choose-lead-mrna-vaccine-candidate-0">codes for</a> the virus’ full-length spike protein.</p>
<p>In <a href="https://clinicaltrials.gov/ct2/show/NCT04380701">early clinical trials</a>, the vaccine was generally safe with no serious side-effects. The vaccine also produced a <a href="https://pubmed.ncbi.nlm.nih.gov/33053279/">robust immune response</a> after two doses.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/367656/original/file-20201105-24-155ysu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Illustration of single-stranded RNA" src="https://images.theconversation.com/files/367656/original/file-20201105-24-155ysu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/367656/original/file-20201105-24-155ysu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/367656/original/file-20201105-24-155ysu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/367656/original/file-20201105-24-155ysu.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/367656/original/file-20201105-24-155ysu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/367656/original/file-20201105-24-155ysu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/367656/original/file-20201105-24-155ysu.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Vaccines based on RNA use your cells’ protein factories to make viral protein, which stimulates your immune system.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/single-strand-ribonucleic-acid-rna-research-1094792225">Shutterstock</a></span>
</figcaption>
</figure>
<p>When older adults (65-85 years of age) were vaccinated, they produced a <a href="https://pubmed.ncbi.nlm.nih.gov/33053279/">greater neutralising antibody response</a> than seen in patients who contracted SARS-CoV-2 naturally.</p>
<p>Interestingly, BNT162b2 is one of the first COVID-19 vaccines to be tested <a href="https://www.pfizer.com/science/coronavirus/vaccine">in adolescents</a> (12-18 years of age).</p>
<p><a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-choose-lead-mrna-vaccine-candidate-0">In July</a>, Pfizer announced the launch of large-scale phase 2/3 trials. Trials are under way in <a href="https://www.health.gov.au/sites/default/files/documents/2020/11/coronavirus-covid-19-information-about-the-pfizer-biontech-vaccine-for-covid-19.pdf">several countries</a>, including the United States, Germany, Argentina, Brazil and South Africa, involving 44,000 participants. </p>
<p>One of the challenges facing this vaccine is distribution, as it needs to be stored below -70°C. This is costly and makes transportation difficult, particularly in developing regions. </p>
<p>If BNT162b2 is successful, <a href="https://www.pm.gov.au/media/australia-secures-further-50-million-doses-covid-19-vaccine">10 million doses</a> <a href="https://www.health.gov.au/sites/default/files/documents/2020/11/coronavirus-covid-19-information-about-the-pfizer-biontech-vaccine-for-covid-19.pdf">will be available</a> in Australia from early 2021.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/australias-just-signed-up-for-a-shot-at-9-covid-19-vaccines-heres-what-to-expect-146750">Australia's just signed up for a shot at 9 COVID-19 vaccines. Here's what to expect</a>
</strong>
</em>
</p>
<hr>
<h2>What happens next?</h2>
<p>Both vaccines, if successful in clinical trials, will be manufactured outside Australia. </p>
<p>This will <a href="https://theconversation.com/australia-may-miss-out-on-several-covid-vaccines-if-it-cant-make-mrna-ones-locally-148996">allay fears</a> Australia might miss out on mRNA vaccines as the country does not have the technology and capacity to make these vaccines itself.</p>
<p>A successful COVID-19 vaccine will also need to navigate the rigorous assessment and approval processes of the Therapeutic Goods Administration for use in Australia.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/australia-may-miss-out-on-several-covid-vaccines-if-it-cant-make-mrna-ones-locally-148996">Australia may miss out on several COVID vaccines if it can't make mRNA ones locally</a>
</strong>
</em>
</p>
<hr>
<h2>Hedging our bets</h2>
<p>It is unlikely all COVID-19 vaccines currently in development will be successful. We have already seen COVID-19 vaccine trials <a href="https://theconversation.com/the-oxford-vaccine-trial-has-been-paused-but-this-is-no-reason-to-panic-145882">temporarily halted</a> due to safety issues. And not all vaccines will provide a consistent level of immunity. Some vaccines may only provide immunity for limited periods of time and require a booster shot.</p>
<p>By investing in numerous front-running candidates, the Australian government’s strategy of not putting all its eggs in one basket is a wise one. </p>
<p>Investing in a range of vaccine technologies also has benefits, should more than one vaccine become available. This is because different vaccine technologies may be more effective or safe in different populations. This increases the likelihood all sections of society — young and old, with or without existing medical complications — could be targeted.</p><img src="https://counter.theconversation.com/content/149522/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Adam Taylor receives funding from The National Health and Medical Research Council of Australia, the National Foundation for Medical Research and Innovation and the New South Wales Department of Primary Industries. </span></em></p>Two more COVID-19 vaccines may now be on the cards for Australia, should they pass clinical trials. But, as with earlier vaccine deals, there are no guarantees.Adam Taylor, Early Career Research Leader, Emerging Viruses, Inflammation and Therapeutics Group, Menzies Health Institute Queensland, Griffith UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1464042020-10-23T02:04:11Z2020-10-23T02:04:11ZChildren may need to be vaccinated against COVID-19 too. Here’s what we need to consider<figure><img src="https://images.theconversation.com/files/364632/original/file-20201021-13-161k9m9.jpg?ixlib=rb-1.1.0&rect=1%2C5%2C997%2C660&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/vaccination-concept-female-doctor-vaccinating-cute-1419146978">Shutterstock</a></span></figcaption></figure><p>An ideal COVID-19 vaccine would not only protect people from becoming ill, it would also stop the virus spreading through the population. The best way to do this is to vaccinate as many people as possible. </p>
<p>If the best available vaccine is only moderately protective — for example, if it only prevents 50% of infections — we might need to vaccinate children as well as adults to interrupt the spread.</p>
<p>There is no COVID-19 vaccine being developed specifically for children. So if children are to be vaccinated, they will likely receive the same vaccine as adults. They might require a different dosing schedule, but that is not yet clear.</p>
<p>So what are the issues with developing a safe and effective COVID-19 vaccine for children? And where are we up to with clinical trials including them?</p>
<h2>Why children?</h2>
<p>Children <a href="https://www.health.gov.au/resources/publications/coronavirus-covid-19-and-children">don’t appear to be “super-spreaders”</a> of COVID-19, although they can still be infected. And if infected, they have a <a href="https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1095/5885157">lower risk of severe illness or death</a> than adults. </p>
<p>However, some children may have a higher risk of severe illness, <a href="https://jamanetwork.com/journals/jamapediatrics/article-abstract/2766037">such as those with existing medical problems</a>. We are also learning more about a rare but <a href="https://www.abc.net.au/news/2020-09-04/pims-ts-kawasaki-covid-19-children-disease-australia-explained/12627610">serious inflammatory condition</a> reported in some children after COVID-19 infection.</p>
<p>There is also a broader issue at stake. Delaying children’s access to vaccines could delay our recovery from COVID-19. This would prolong <a href="https://www.unicef.org.au/blog/unicef-in-action/may-2020/coronavirus-hidden-impacts">the pandemic’s considerable impact</a> on children’s education, health and emotional well-being.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/rare-multisystem-inflammatory-syndrome-in-children-linked-to-coronavirus-140152">Rare multisystem inflammatory syndrome in children linked to coronavirus</a>
</strong>
</em>
</p>
<hr>
<h2>Would children react differently to a vaccine?</h2>
<p>The way a child’s immune system reacts to pathogens or vaccines can be different to adults. Age can determine the number of required doses. For example, infants sometimes require more doses of a vaccine than older children.</p>
<p>Age can also influence the side-effect profile of a vaccine. For example, <a href="http://www.talkingaboutimmunisation.org.au/common-reactions">mild fever following vaccination</a> can be common in babies and young children.</p>
<p>So vaccine developers need to include children in their clinical trials so they can gather age-specific information on the immune response, the effectiveness of the vaccine in preventing disease, and any side-effects.</p>
<h2>Are COVID-19 vaccines already being tested in children?</h2>
<p>Vaccine trials are usually <a href="http://ncirs.org.au/phases-clinical-trials">done in stages</a>. They typically start with healthy, young and middle-aged adults. </p>
<p>Once a vaccine is confirmed to be safe in these earlier trials, developers then test the vaccine in older and younger age groups.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/362621/original/file-20201009-21-2xdde3.jpg?ixlib=rb-1.1.0&rect=0%2C7%2C1000%2C658&q=45&auto=format&w=1000&fit=clip"><img alt="Children playing outside under a colourful parachute" src="https://images.theconversation.com/files/362621/original/file-20201009-21-2xdde3.jpg?ixlib=rb-1.1.0&rect=0%2C7%2C1000%2C658&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/362621/original/file-20201009-21-2xdde3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/362621/original/file-20201009-21-2xdde3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/362621/original/file-20201009-21-2xdde3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/362621/original/file-20201009-21-2xdde3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/362621/original/file-20201009-21-2xdde3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/362621/original/file-20201009-21-2xdde3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Some vaccine developers have already announced plans to test their COVID-19 vaccines in children.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/joyous-classmates-jumping-under-colorful-parachute-1140503744">Shutterstock</a></span>
</figcaption>
</figure>
<p>Several COVID-19 vaccine developers already have plans to include children in their clinical trials. </p>
<p>University of Oxford researchers <a href="https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001228-32/GB">will recruit</a> children aged 5-12 into a phase 2/3 trial of its vaccine. This is one of the vaccines for which the Australian government has a <a href="https://theconversation.com/morrison-government-secures-two-possible-vaccine-supplies-with-agreements-worth-1-7-billion-145678">supply agreement</a>, should clinical trials prove successful.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/putting-our-money-on-two-covid-vaccines-is-better-than-one-why-australias-latest-vaccine-deal-makes-sense-145693">Putting our money on two COVID vaccines is better than one: why Australia's latest vaccine deal makes sense</a>
</strong>
</em>
</p>
<hr>
<p>Pfizer will enrol children <a href="https://www.pfizer.com/science/coronavirus/vaccine">aged 12 and older</a> in a phase 2/3 trial of its vaccine. <a href="https://clinicaltrials.gov/ct2/show/NCT04566770?term=vaccine&cond=covid-19&draw=7">Multiple developers</a> in <a href="http://www.chictr.org.cn/showprojen.aspx?proj=52227">China</a> and <a href="http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=45306&EncHid=&userName=vaccine">in</a> <a href="https://clinicaltrials.gov/ct2/show/NCT04471519?term=bharat&cond=covid-19&draw=2&rank=1">India</a> are also including children in COVID-19 vaccine trials, some as young as <a href="https://clinicaltrials.gov/ct2/show/NCT04566770?term=vaccine&cond=covid-19&draw=7">six</a>.</p>
<p>All of these trials are ongoing and have not released results.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/from-adenoviruses-to-rna-the-pros-and-cons-of-different-covid-vaccine-technologies-145454">From adenoviruses to RNA: the pros and cons of different COVID vaccine technologies</a>
</strong>
</em>
</p>
<hr>
<h2>How could we get more children included in trials?</h2>
<p>We need more children included in clinical trials, an issue recognised globally. For instance, the US Food and Drug Administration <a href="https://www.fda.gov/media/137926/download">announced</a> it will work as quickly as possible with vaccine developers to set up trials for COVID-19 vaccines in children. </p>
<p>The US National Institutes of Health <a href="https://www.wired.com/story/making-a-covid-19-vaccine-is-hard-making-one-for-kids-is-harder">is developing</a> a protocol for researchers to include children in vaccine trials in a safe but timely way. </p>
<p>Having a universal protocol, which we don’t yet have for COVID-19 vaccine trials, would make it easier for researchers to include children in future trials, and to compare different vaccines.</p>
<p>There are no protocols yet including children in COVID-19 vaccine trials run in Australia. Any Australian studies would only likely examine the immune response and safety in children (phase 1 and 2 trials). They would probably not examine effectiveness (phase 3 trials) because of the low rates of COVID-19 here.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/how-researchers-assess-whether-medications-work-102773">How researchers assess whether medications work</a>
</strong>
</em>
</p>
<hr>
<p>Before any child is enrolled in a trial their parent or guardian will be asked to read an information sheet that explains the <a href="https://www.australianclinicaltrials.gov.au/why-be-part-clinical-trial/clinical-trials-and-children">risks and benefits of taking part</a>. Safety data from earlier trials in adults would need to be included in child-specific information sheets, so parents are aware of the known risks before they decide to enrol their child. </p>
<p>In Australia, it may be a challenge to enrol children in COVID-19 vaccine trials, as the disease burden is low compared with other countries, so parents may not want their child to take part. </p>
<p>However, it is important we learn as much as we can about how COVID-19 vaccines perform in children, and participating in such research helps us gather this valuable information.</p>
<h2>How is vaccine safety assessed?</h2>
<p>Vaccine trials are closely supervised by an independent <a href="https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwiZ9qjDssTsAhUJwTgGHf37CXIQFjAAegQIARAC&url=https%3A%2F%2Fwww.australianclinicaltrials.gov.au%2Fsites%2Fdefault%2Ffiles%2Fcontent%2FFor%2520researchers%2FData%2520Safety%2520Monitoring%2520Boards_1.pdf&usg=AOvVaw3mJ3Oh43BIMTO3zbElhuhn">data and safety monitoring board</a>, who follow strict protocols and have the authority to pause a trial if there are safety issues.</p>
<p>Australia also has strict <a href="https://www.tga.gov.au/vaccines-overview">guidelines for the registration of vaccines</a>. A vaccine will only be licensed if its safety has been demonstrated in large studies, usually including many thousands of people. Usually, vaccines are registered according to the age groups in which trials have been done.</p>
<p>Even after a vaccine is licensed in Australia, its <a href="https://www.tga.gov.au/vaccines-overview">safety continues to be monitored</a>. A doctor, patient or parent can report side-effects to the authorities.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/halting-the-oxford-vaccine-trial-doesnt-mean-its-not-safe-it-shows-theyre-following-the-right-process-145837">Halting the Oxford vaccine trial doesn't mean it's not safe – it shows they're following the right process</a>
</strong>
</em>
</p>
<hr>
<p>Alternatively, researchers can more actively engage with the public to monitor side-effects, such as with the <a href="http://www.ausvaxsafety.org.au/">AusVaxSafety</a> system. </p>
<p>In this system, when a GP gives someone a vaccine, that person receives a text message three days later to ask about side-effects and to complete a survey on their smart phone or computer. This is “real time”, important safety data. </p>
<p>We already use this system to monitor the safety of each year’s flu vaccines and will potentially use it when COVID-19 vaccines are rolled out into the community.</p>
<h2>In a nutshell</h2>
<p>Although there has been extraordinary progress in COVID-19 vaccine trials, only some vaccine developers have taken steps to recruit children so far. That needs to change if we are to protect children and the wider community. So we need protocols that make it easier for researchers to recruit children into COVID-19 vaccine trials.</p>
<p>As early data in adults accumulates, providing information to parents — and where age-appropriate, their children — to consent to their child participating in trials has a lot of benefits. It will also ultimately help us in the race to end this pandemic.</p><img src="https://counter.theconversation.com/content/146404/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Kristine Macartney is the Director of NCIRS and the organisation she works for receives funding from Australian and state Governments, the NHMRC and other non-commercial sources. </span></em></p><p class="fine-print"><em><span>Nicholas Wood receives funding from NHMRC for a Career Development Fellowship</span></em></p><p class="fine-print"><em><span>Ketaki Sharma does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Any COVID-19 vaccine is likely to be given first to higher risk groups before it is given to children. But we still need vaccines that are safe and effective for them too.Ketaki Sharma, PhD student, University of SydneyKristine Macartney, Professor, Discipline of Paediatrics and Child Health, University of SydneyNicholas Wood, Associate Professor, Discipline of Childhood and Adolescent Health, University of SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1484702020-10-21T22:26:40Z2020-10-21T22:26:40ZCoronavirus vaccine trials won’t tell us if they save lives, prevent serious illness or stop transmission – here’s why<p>There are currently at least six COVID-19 vaccines in phase 3 clinical trials – the final phase of testing. These trials all aim to compare the safety and effectiveness of the vaccines versus a placebo. However, as Peter Doshi, associate editor at the BMJ, asks in a <a href="https://www.bmj.com/content/371/bmj.m4037">new report</a>, what does “effective” actually mean?</p>
<p>The primary goal of these phase 3 trials in progress is to determine whether the vaccine reduces the risk of a person getting symptomatic COVID-19. To be counted as a COVID-19 case, trial participants must have a positive swab test, as well as a defined list of symptoms – which varies from one trial to another. These symptoms can range from a mild headache through to severe disease requiring intensive care.</p>
<p>Each trial uses their own definition of a positive case to estimate how many people are expected to get COVID-19 in the control group (those not receiving the experimental vaccine). For example, the <a href="https://www.modernatx.com/sites/default/files/mRNA-1273-P301-Protocol.pdf">Moderna vaccine clinical trial protocol</a> works on the assumption that one out of 133 people will develop symptomatic COVID-19 over a six-month period. If the vaccine is 60% effective, then complex statistical analysis dictates that only 151 people out of 30,000 recruits need to become symptomatically infected for this degree of protection to be apparent.</p>
<h2>Cause for concern?</h2>
<p>Concern has been raised that by following this type of trial design, it won’t be possible to tell whether a vaccine protects against severe disease or death. Indeed, the design of these first trials does not differentiate mild from severe cases of COVID-19 in the primary analysis, but there are very good reasons for this and it should not be a cause for alarm.</p>
<p>Quite simply, many fewer people die from COVID-19 than develop mild symptoms of disease. To prove that a vaccine protects against only severe or fatal cases would require many more people to be recruited to each trial. With trials already involving tens of thousands of participants, this is just not realistic at this stage. </p>
<p>Trials testing severe disease or death alone as an endpoint would need much more time and money to be completed. So designing these first phase 3 trials has been a balancing act: being able to show whether some degree of protection is achieved while delivering these results in the most timely manner.</p>
<p>Also, whereas the severity of disease is not the focus of trial outcome, all ongoing trials are still carefully monitoring the severity of all COVID-19 cases. Valuable conclusions can still be drawn from this data, even if statistical significance cannot be proved.</p>
<p>Another issue that has been raised regarding current phase 3 clinical trials has been the fact that the people who most need protecting, such as the elderly and those with compromised immune systems (such as people undergoing chemotherapy), are not being recruited. But this is a standard recruitment approach for any clinical trial, so it is not unexpected. It does mean that the conclusions drawn about vaccine efficacy may not directly apply to those people excluded from trials. Still, a vaccine that can reduce symptomatic COVID-19 in healthy adults is essential, as it will reduce the risk of infection of vulnerable groups.</p>
<p>It is important to be aware of the limitations of the current trials, but these should not be considered as major flaws. The aim of any clinical trial is to examine a subset of the population to make the best guess as to what will happen if the entire population is treated the same way. </p>
<p>Ultimately, only when the whole population is vaccinated can the exact efficacy of a vaccine be determined. Coronavirus vaccine trials are, therefore, expected to continue for years to come, each one contributing to our understanding of how to control this virus.</p><img src="https://counter.theconversation.com/content/148470/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sarah L Caddy does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Coronavirus trial protocols have only recently been released. This is what they show.Sarah L Caddy, Clinical Research Fellow in Viral Immunology and Veterinary Surgeon, University of CambridgeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1474142020-10-14T16:51:35Z2020-10-14T16:51:35ZExcluding pregnant women from COVID-19 vaccine trials puts their health at risk<figure><img src="https://images.theconversation.com/files/362550/original/file-20201008-18-1cq93qp.jpg?ixlib=rb-1.1.0&rect=20%2C0%2C6689%2C4456&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Pregnant women are routinely excluded from clinical trials for drugs and vaccines.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>With no effective cure and limited treatment options, the <a href="https://jamanetwork.com/journals/jama/fullarticle/2768156">development of safe and effective vaccines for COVID-19 is a high priority.</a> Vaccines both protect individuals against infection and reduce community spread of the virus by interrupting transmission pathways.</p>
<p>Once safe and effective vaccines for COVID-19 are available, the challenge will be to ensure their <a href="https://apps.who.int/iris/bitstream/handle/10665/334299/WHO-2019-nCoV-SAGE_Framework-Allocation_and_prioritization-2020.1-eng.pdf">fair distribution across and within countries</a>. In addition to global equitable access, fair priorities will need to be set within jurisdictions. Immediate priority groups will likely include health-care workers, personal care attendants, first responders, adults over age 65 and other high-risk adults with existing health conditions. But after that, groups that need consideration include pregnant women.</p>
<h2>COVID-19 in pregnancy</h2>
<p>While there is limited data on the prevalence and severity of COVID-19 among pregnant women, it is thought that they could be at risk of serious complications from COVID-19. <a href="https://www.cdc.gov/mmwr/volumes/69/wr/mm6925a1.htm">One study in the United States</a> found that infected pregnant women were 1.5 times more likely to be admitted to the intensive care unit and 1.7 times more likely to receive mechanical ventilation than infected non-pregnant women. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/362267/original/file-20201007-18-17jc0m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A smiling woman holds up a strip of sonogram images." src="https://images.theconversation.com/files/362267/original/file-20201007-18-17jc0m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/362267/original/file-20201007-18-17jc0m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=434&fit=crop&dpr=1 600w, https://images.theconversation.com/files/362267/original/file-20201007-18-17jc0m.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=434&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/362267/original/file-20201007-18-17jc0m.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=434&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/362267/original/file-20201007-18-17jc0m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=545&fit=crop&dpr=1 754w, https://images.theconversation.com/files/362267/original/file-20201007-18-17jc0m.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=545&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/362267/original/file-20201007-18-17jc0m.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=545&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">In this June 2020 photo, Astrid Galvan poses for a photo with her sonogram for her second child in Phoenix.</span>
<span class="attribution"><span class="source">(AP Photo/Astrid Galvan)</span></span>
</figcaption>
</figure>
<p><a href="https://www.thelancet.com/pdfs/journals/eclinm/PIIS2589-5370(20)30190-5.pdf">A systemic review and meta-analysis</a> that included 17 studies (2,567 pregnancies) found that admission to the intensive care unit was required in seven per cent of cases, whereas the rate of admission for infected non-pregnant women was 4.2 per cent. This review also confirmed an increased risk of preterm birth and delivery by caesarean section.</p>
<p>These facts, as well as the likelihood that pregnant women’s access to drug therapies for COVID-19 may be restricted (as is the case for most drug therapies during pregnancy), suggest that pregnant women <a href="https://www.thelancet.com/action/showPdf?pii=S1473-3099%2820%2930638-1">should be a target population for COVID-19 vaccine research</a>. And yet, the default position for both drug and vaccine research is to exclude pregnant women from research participation because of risks to the pregnant women and their offspring.</p>
<p><a href="https://www.springer.com/gp/book/9783319265100">Two major tragedies</a> — thalidomide prescribed for morning sickness during the 1950s and diethylstilbestrol (DES) prescribed to prevent miscarriage from the 1940s to the 1970s — cemented the view that pregnant women and their offspring were vulnerable and should be protected from research risk. Ironically, while both these cases involved harm arising in the clinical setting due to a lack of adequate prior clinical research, the result has been to systematically exclude pregnant women from clinical trials.</p>
<h2>The risks of exclusion</h2>
<p>The lack of evidence that a vaccine is safe and can provoke an immune response in pregnant women <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2747530/">undermines effective decision-making for both clinicians and pregnant women</a>, possibly resulting in the use of unsafe vaccines. Without research, pregnant women and their offspring are exposed to the avoidable risks of off-label and compassionate use of non-evidence-based vaccinations. </p>
<p>Exclusion from research does not dodge the risk of unproven vaccinations; it simply shifts this risk from a carefully monitored clinical trial to the privacy of a doctor’s office. Excluding pregnant women from vaccine research is both unjust and imprudent from a public health perspective.</p>
<figure class="align-center ">
<img alt="Silhouette of a pregnant woman against an illustration of a coronavirus." src="https://images.theconversation.com/files/362562/original/file-20201008-24-bigufe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/362562/original/file-20201008-24-bigufe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=597&fit=crop&dpr=1 600w, https://images.theconversation.com/files/362562/original/file-20201008-24-bigufe.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=597&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/362562/original/file-20201008-24-bigufe.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=597&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/362562/original/file-20201008-24-bigufe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=750&fit=crop&dpr=1 754w, https://images.theconversation.com/files/362562/original/file-20201008-24-bigufe.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=750&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/362562/original/file-20201008-24-bigufe.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=750&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">In a study, pregnant women with COVID-19 were 1.5 times more likely to be admitted to the intensive care unit and 1.7 times more likely to receive mechanical ventilation than infected non-pregnant women.</span>
<span class="attribution"><span class="source">(Pixabay/Canva)</span></span>
</figcaption>
</figure>
<p>Last year, the Pregnancy Research Ethics for Vaccines, Epidemics, and New Technologies (PREVENT) Working Group issued a <a href="https://doi.org/10.1016/j.vaccine.2019.01.011">Guidance on Pregnant Women and Vaccines Against Emerging Epidemic Threats: Ethics Guidance for Preparedness, Research and Response</a>. This guidance is grounded in the belief that “pregnant women cannot be ignored as the scientific and biomedical communities continue to innovate and develop new medicines and tools to improve health.” It provides a generic “road map for the ethically responsible, socially just and respectful inclusion of the interests of pregnant women in the development and deployment of vaccines against emerging pathogens.”</p>
<h2>COVID-19 vaccine trials</h2>
<p><a href="https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html">Forty-four candidate vaccines for COVID-19 are currently in human clinical trials</a>: 29 in Phase 1, 14 in Phase 2 and 11 in Phase 3 trials. Phase 1 trials focus on safety and dosage and typically recruit a small number of research participants. Phase 2 trials continue to gather information about adverse events and immune response and usually involve hundreds of people. </p>
<p>Phase 3 randomized controlled trials involve tens of thousands of healthy volunteers where some are immunized with the candidate vaccine and others receive a placebo. The goal is to determine if persons who are vaccinated are protected from infection. If the candidate vaccine proves safe and effective, then it can be licensed for use in the general population.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/explainer-how-clinical-trials-test-covid-19-vaccines-146061">Explainer: How clinical trials test COVID-19 vaccines</a>
</strong>
</em>
</p>
<hr>
<p>It is reported that, to date, <a href="https://www.reuters.com/article/us-health-coronavirus-vaccines-pregnancy/large-u-s-covid-19-vaccine-trials-will-exclude-pregnant-women-for-now-idUSKCN24W1NZ">Johnson & Johnson, Moderna and Pfizer</a>, all of whom have started Phase 3 clinical trials, have indicated an interest in future vaccine trials involving pregnant women, possibly in early 2021. A problem with including pregnant women in the Moderna or Pfizer trials is that their vaccines use an <a href="https://www.bloomberg.com/features/2020-moderna-biontech-covid-shot/">unproven gene-based technology</a>. </p>
<p>To minimize the risk of harm to pregnant women and their offspring, the vaccines tested in this population should be ones that use a more established technology. The Johnson & Johnson COVID-19 vaccine uses the <a href="https://abcnews.go.com/Health/johnson-johnson-4th-manufacturer-begin-phase-trials-covid/story?id=73192679">same technology as their Ebola vaccine</a>, which has been given to pregnant women.</p>
<h2>Including pregnant women in trials</h2>
<p>Moving from the general to the specific, there are at least <a href="https://www.openaccessjournals.com/articles/research-involving-pregnant-women-trials-and-tribulations.pdf">two scientifically valid options for the inclusion of pregnant women in vaccine trials</a>. One option involves standalone Phase 1 trials for pregnant women that would be initiated following the successful completion of Phase 1 and 2 studies in the general population and the start of Phase 3 studies in this population. </p>
<p>This approach allows for greater clarity in trial design and ease in safety monitoring during the clinical trial because only pregnant women are included and end points can be specifically defined for pregnant women and their offspring. A pregnancy-specific trial could increase the likelihood of effective pregnancy-related risk counselling and informed consent processes, involvement of investigators with relevant expertise and effective followup.</p>
<p>Alternatively, Phase 1 vaccine trials for pregnant women could be embedded into Phase 3 trials in the general population. This approach entails reduced startup costs compared to initiating a separate trial, given the main trial protocols, infrastructure, staff, monitoring arrangement and regulatory approval will already have been established.</p>
<p>Pregnant women and their offspring must not be left behind in the race to develop safe and effective vaccines for COVID-19.</p><img src="https://counter.theconversation.com/content/147414/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Pregnant women are at increased risk for serious COVID-19 complications and should be a high-priority group for vaccination. Excluding them from vaccine trials puts them and their offspring at risk.Angela Ballantyne, Senior Visiting Research Fellow in Bioethics, National University of SingaporeFrançoise Baylis, Research Professor, Philosophy, Dalhousie UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1473492020-10-12T18:48:30Z2020-10-12T18:48:30ZInfecting volunteers with coronavirus may be one way to test potential vaccines. But there are risks<figure><img src="https://images.theconversation.com/files/362580/original/file-20201009-20-18e7t2q.jpg?ixlib=rb-1.1.0&rect=20%2C7%2C977%2C655&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/doctor-injecting-vaccine-covid19-young-man-1825720982">Shutterstock</a></span></figcaption></figure><p>Researchers are considering using “human challenge studies” to accelerate COVID-19 vaccine research and development. This would involve giving an experimental vaccine to healthy volunteers, then deliberately exposing them to the virus to see whether they’re protected from infection. </p>
<p><a href="https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30438-2/fulltext">Challenge studies</a> can also allow scientists to monitor the progress of infectious diseases from the moment they begin, and to study infection and immunity more closely than other types of research.</p>
<p>These studies can answer scientific questions in a short time. They recruit small numbers of participants — up to around 100 volunteers per study — usually young, healthy adults.</p>
<p>However, deliberate infection with SARS-CoV-2, the virus that causes COVID-19, <a href="https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1290/5898660">involves risks</a> to volunteers.</p>
<h2>How do these studies differ from standard, larger studies?</h2>
<p>Standard “field” trials for some COVID-19 vaccine candidates have <a href="https://clinicaltrials.gov/ct2/show/NCT04516746">already begun</a>. Each aims to recruit at least 10,000 people. Usually, half or two-thirds receive the experimental vaccine and the rest might receive a placebo or a vaccine against another disease. </p>
<p>Participants then go about their daily lives. Scientists observe whether those who received the COVID-19 vaccine are less frequently infected with the virus than the other group, allowing them to determine how effective the vaccine is. </p>
<figure class="align-center ">
<img alt="Two scientists in a lab look at a syringe." src="https://images.theconversation.com/files/362859/original/file-20201012-16-sgsc46.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/362859/original/file-20201012-16-sgsc46.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/362859/original/file-20201012-16-sgsc46.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/362859/original/file-20201012-16-sgsc46.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/362859/original/file-20201012-16-sgsc46.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/362859/original/file-20201012-16-sgsc46.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/362859/original/file-20201012-16-sgsc46.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Human challenge studies involve fewer participants than standard field trials.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<p>In large epidemics, field trials can quickly reveal whether a vaccine works. But proof may be delayed <a href="https://link.springer.com/article/10.1007%2Fs11673-020-10030-x">when there’s less community transmission</a>, for example due to local public health measures.</p>
<p>If current field trials identify a highly effective vaccine, there might be less need for human challenge trials. However, if the first vaccines fail, or turn out to be only moderately effective, challenge studies could be used to select the next most promising candidates for future field trials.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/from-adenoviruses-to-rna-the-pros-and-cons-of-different-covid-vaccine-technologies-145454">From adenoviruses to RNA: the pros and cons of different COVID vaccine technologies</a>
</strong>
</em>
</p>
<hr>
<h2>Challenge studies need extra preparation</h2>
<p>First, scientists need to prepare a strain of SARS-CoV-2 in the laboratory to administer to volunteers. The strain needs to be similar to the virus circulating in the community. </p>
<p>There’s also a need for special research facilities with health-care support and capacity to isolate participants. </p>
<p>Volunteers may have to remain in these facilities for 2–3 weeks to be closely monitored, and so they are not released into the community while they may be infectious.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/coronavirus-why-i-support-the-worlds-first-covid-vaccine-challenge-trial-146809">Coronavirus: why I support the world's first COVID vaccine challenge trial</a>
</strong>
</em>
</p>
<hr>
<h2>Past experience and recent developments</h2>
<p>While COVID-19 challenge trials are now <a href="https://www.bbc.com/news/health-54275096">making news</a>, scientists have previously conducted these kinds of experiments with many <a href="https://www.springer.com/gp/book/9783030414795">different types of microorganisms</a>. </p>
<p>Such studies <a href="https://www.the-scientist.com/news-opinion/a-challenge-trial-for-covid-19-would-not-be-the-first-of-its-kind-68030">have been used</a> to develop vaccines against malaria, typhoid and cholera. They have also provided unique insights into immunity to <a href="https://mbio.asm.org/content/7/2/e00417-16">influenza</a> and “common cold” <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2425374/">coronaviruses</a>.</p>
<p>One research centre in London has announced a <a href="https://www.openorphan.com/covid-19">plan to conduct challenge studies</a> with SARS-CoV-2. Another centre in the United States is also <a href="https://www.reuters.com/article/us-health-coronavirus-vaccine-challenge-idUSKCN25A1EL">preparing a strain</a> of the virus.</p>
<h2>Ethical and scientific questions</h2>
<p>The World Health Organisation (WHO) convened two advisory groups, in which we were involved, to consider COVID-19 human challenge studies. One focused on ethics, the other on scientific and technical aspects.</p>
<p>The ethics group identified <a href="https://www.who.int/ethics/publications/key-criteria-ethical-acceptability-of-covid-19-human-challenge/en/">eight criteria</a> proposed challenge studies would need to meet before going ahead. </p>
<p>These included the need for researchers to consult and engage with the general public before, during, and after the trials. There would also need to be careful independent expert review, and demonstration that expected benefits are likely to outweigh risks. </p>
<p>Relevant risks might be especially hard to predict for SARS-CoV-2, partly because it’s a new pathogen. </p>
<p>While young, healthy people generally fare better with COVID-19 than older adults with pre-existing conditions, there are exceptions. For example, a <a href="https://www.cdc.gov/mmwr/volumes/69/wr/mm6940e1.htm">multisystem inflammatory syndrome</a> has been reported in rare cases among previously healthy adults after they contracted COVID-19.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/infecting-healthy-people-in-vaccine-research-can-be-ethical-and-necessary-116263">Infecting healthy people in vaccine research can be ethical and necessary</a>
</strong>
</em>
</p>
<hr>
<p>Members of WHO’s <a href="https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1290/5898660">science group</a> agreed on a number of technical requirements for COVID-19 challenge studies to maximise volunteers’ safety and prevent wider spread of infection.</p>
<p>These included recruiting only healthy young adults, conducting the studies under strict biosafety procedures (for example, isolating participants), giving the virus via the nose to mimic natural infection, and carefully increasing the dose of the virus.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/362583/original/file-20201009-22-f74m5e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Group of young adult students outside looking at books and papers, studying" src="https://images.theconversation.com/files/362583/original/file-20201009-22-f74m5e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/362583/original/file-20201009-22-f74m5e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/362583/original/file-20201009-22-f74m5e.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/362583/original/file-20201009-22-f74m5e.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/362583/original/file-20201009-22-f74m5e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/362583/original/file-20201009-22-f74m5e.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/362583/original/file-20201009-22-f74m5e.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Only young adults without underlying health conditions could volunteer for these studies.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/group-friends-studying-together-university-campus-550396426">Shutterstock</a></span>
</figcaption>
</figure>
<p>However, the experts were split on other issues, such as whether:</p>
<ul>
<li><p>challenge studies would actually accelerate vaccine approval</p></li>
<li><p>results in young healthy adults would demonstrate whether or not a vaccine works for older people</p></li>
<li><p>challenge trials should begin before a proven and highly effective treatment for COVID-19 becomes available.</p></li>
</ul>
<h2>What next?</h2>
<p>To design an ethically acceptable challenge study, it’s important to <a href="https://jme.bmj.com/content/early/2020/09/25/medethics-2020-106504">minimise the risks</a> to study volunteers, research staff, and the wider community.</p>
<p>In the future, there may be additional ways scientists can reduce the risks. They may be able to better identify those at lowest risk of severe infection, develop a weakened strain of the virus, or have a highly effective treatment on hand to use if needed.</p>
<p>In the meantime, scientists could obtain results relevant to COVID-19 by conducting less risky challenge studies with other viruses.</p>
<p>For example, challenge studies with “common cold” coronaviruses, which are being considered in Australia, could teach us about the types of immune responses that protect us against coronavirus diseases.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/australias-just-signed-up-for-a-shot-at-9-covid-19-vaccines-heres-what-to-expect-146750">Australia's just signed up for a shot at 9 COVID-19 vaccines. Here's what to expect</a>
</strong>
</em>
</p>
<hr>
<p>Research eventuating in safe and effective vaccines for COVID-19 could save many lives. However, whether the benefits of challenge studies in the current pandemic outweigh the risks depends on many factors.</p>
<p>We must carefully consider proposals for these studies in light of the current state of science and vaccine development, and update our evaluations as new data emerge.</p><img src="https://counter.theconversation.com/content/147349/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Euzebiusz Jamrozik was a member of two World Health Organization Advisory Groups on Covid-19 human challenge studies. He has received funding from the Wellcome Trust and WHO for projects on the ethics of human infection challenge studies, and his fellowship at the University of Oxford is supported by the Wellcome Trust (203132/Z/16/Z), (216355/Z/19/Z).</span></em></p><p class="fine-print"><em><span>Kanta Subbarao was a member of a World Health Organization Advisory Group on COVID-19 challenge studies. She has received funding from the NHMRC, MRFF, Victorian DHHS and NIH. </span></em></p><p class="fine-print"><em><span>Michael Selgelid was a member of the WHO Working Group for Guidance on Human Challenge Studies in COVID-19. He has received funding from The Wellcome Trust for previous research on the ethics of human infection challenge studies.</span></em></p>There are many scientific and ethical challenges ahead. But these types of trials have helped in the development of vaccines against a few diseases. Could they do the same for COVID-19?Euzebiusz Jamrozik, Infectious Disease Ethics Fellow, Ethox & Wellcome Centre for Ethics and Humanities, Univeristy of Oxford. Adjunct, Monash UniversityKanta Subbarao, Professor, The Peter Doherty Institute for Infection and ImmunityMichael Selgelid, Professor of Bioethics, Monash Bioethics Centre, Monash University, Monash UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1460912020-09-22T18:59:19Z2020-09-22T18:59:19ZHow and when will we know that a COVID-19 vaccine is safe and effective?<figure><img src="https://images.theconversation.com/files/358194/original/file-20200915-20-141c8is.jpg?ixlib=rb-1.1.0&rect=26%2C66%2C4415%2C3856&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">How much longer must society wait for a vaccine?</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/hourglass-inside-syringe-artwork-royalty-free-illustration/488635523?adppopup=true">ANDRZEJ WOJCICKI/Getty Images</a></span></figcaption></figure><p>With COVID-19 vaccines currently in the final phase of study, you’ve probably been wondering how the FDA will decide if a vaccine is safe and effective.</p>
<p>Based on the status of the <a href="https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html">Phase 3 trials</a> currently underway, it is unlikely that the results of these trials will be available before November. But it is likely that not just one but several of the competing COVID-19 vaccines will be shown to be safe and effective by the end of 2020. </p>
<p><a href="https://scholar.google.com/citations?hl=en&user=6yMIM1MAAAAJ&view_op=list_works&sortby=pubdate">I am a scientist and infectious diseases specialist</a> at the University of Virginia, where I care for patients with COVID-19 and conduct research on the pandemic. I am also a member of the World Health Organization Expert Group on COVID-19 Vaccine Prioritization. </p>
<h2>What is the status of COVID-19 vaccines in human clinical trials?</h2>
<p><a href="https://partners.mediasite.com/mediasite/Play/968f633a874c4f1a80c368496f49d4661d">Phase 3 studies are underway</a> for the Moderna and BioNTech/Pfizer vaccines, the Oxford/AstraZeneca viral vector vaccine and now the <a href="https://www.washingtonpost.com/health/2020/09/23/coronavirus-vaccine-jj-single-shot/">Johnson & Johnson viral vector vaccine</a>. </p>
<p>Each of these vaccines uses the SARS-CoV-2 spike glycoprotein, which the virus uses to infect cells, to trigger the immune system to generate protective antibodies and a cellular immune response to the virus. Protective antibodies act by preventing the spike glycoprotein from attaching the virus to human cells, thereby neutralizing the SARS-CoV-2 virus that causes COVID-19.</p>
<p>In the case of <a href="https://theconversation.com/coronavirus-a-new-type-of-vaccine-using-rna-could-help-defeat-covid-19-133217">Moderna’s nucleic acid vaccine</a>, the messenger RNA encoding the spike glycoprotein is encased in a fat droplet – called a liposome – to protect the mRNA from degradation and enable it to enter cells. Once these instructions are inside the cells, the mRNA is read by the human cell machinery and made into many spike proteins so that the immune system can respond and begin producing antibodies against this coronavirus. </p>
<p>The Oxford/AstraZeneca and <a href="https://www.jnj.com/johnson-johnson-initiates-pivotal-global-phase-3-clinical-trial-of-janssens-covid-19-vaccine-candidate">Johnson & Johnson</a> vaccines use a different strategy to activate an immune response. Here an adenovirus found in chimpanzees shuttles the instructions for manufacturing the spike glycoprotein into cells.</p>
<p><a href="http://doi.org/10.1126/science.abc5312">Phase 1 and 2 studies by pharmaceutical companies Janssen and Merck</a> also use viral vectors similar to the Oxford/AstraZeneca and J&J vaccines, while vaccines by Novavax and GSK-Sanofi use the actual spike protein itself. </p>
<h2>Animal tests show the vaccines provide protection from coronavirus infection</h2>
<p>Studies in animal models of COVID-19 provide convincing evidence that vaccination with the spike glycoprotein will protect from COVID-19. Experiments have show that when the immune system is shown the spike protein – which alone cannot trigger disease – the immune system will generate an antibody response that protects from infection with SARS-CoV-2.</p>
<p><a href="https://doi.org/10.1038/s41591-020-1070-6">In studies in hamsters</a> an adenovirus viral vector – the approach used by Oxford/AstraZeneca, for example – was used to immunize with the Spike glycoprotein. When the hamsters were infected with SARS-CoV-2 they were protected from pneumonia, weight loss and death.</p>
<p><a href="http://doi.org/10.1126/science.abc6284">In nonhuman primates</a>, DNA vaccines – which deliver the gene for the spike glycoprotein – reduced the amount of virus in the lungs. Animals that produced antibody that prevented virus attachment to human cells were most likely to be protected.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/6iRatByNw08?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">History of vaccines: Smallpox to SARS-CoV-2.</span></figcaption>
</figure>
<h2>What have the early Phase 1 and 2 studies in humans shown?</h2>
<p>Overall, <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2026920?query=featured_coronavirus">vaccination has triggered a more potent neutralizing antibody response</a> than even that seen in patients recovering from COVID-19. </p>
<p>This has also been the case for <a href="http://doi.org/10.1056/NEJMoa2022483">Moderna’s vaccine currently in Phase 3 trials</a> and for vaccines from <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31611-1/fulltext">CanSino Biologics and Oxford/ AstraZeneca.</a> </p>
<h2>What side effects have been observed?</h2>
<p><a href="https://doi.org/10.1016/S0140-6736(20)31605-6">Physicians have recorded</a> <a href="https://doi.org/10.1016/S0140-6736(20)31604-4">mild to moderate reactions</a> <a href="http://doi.org/10.1056/NEJMoa2022483">when the subjects were observed</a> up to 28 days after vaccination. These side effects included mild pain, warmth and tenderness at the site of injection, and fever, fatigue, joint and muscle pain. </p>
<p>But Phase 1 and 2 studies are by small by design, with just hundreds of participants. So these trials will not be large enough to detect uncommon or rare side effects. </p>
<p>The emphasis on safety as the primary goal was recently demonstrated in the Phase 3 Oxford/AstraZeneca vaccine trial <a href="https://www.nature.com/articles/d41586-020-02594-w">where one vaccinated individual developed inflammation of the spinal cord</a>. It isn’t clear whether the vaccine caused this reaction – it might be a new case of multiple sclerosis unrelated to the vaccine – but the Phase 3 trial was halted in the U.S. until more is known.</p>
<h2>How is the FDA ensuring that a vaccine will be safe yet quickly produced?</h2>
<p>The <a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents/development-and-licensure-vaccines-prevent-covid-19">FDA has issued guidance for industry</a> on the steps required for developing and ultimately licensing vaccines to prevent COVID-19 – these are the same rigorous safety standards required for all vaccines.</p>
<p>There are, however, ways to speed the process of approval that are centered on “platform technology.” What this means is that if a vaccine is using an approach such as an adenovirus that has previously been shown to be safe, it may be possible for a company to use previously collected data on toxicity and pharmacokinetics to fast-track clinical trial approval. </p>
<p>While speed and safety may appear conflicting goals, it is also encouraging to note that the <a href="https://www.wsj.com/articles/covid-19-vaccine-developers-prepare-joint-pledge-on-safety-standards-11599257729">rival vaccine manufacturers have jointly pledged</a> not to bow to any political pressures to rush vaccine approval, but to maintain the most rigorous safety standards. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/74WQgNa3OsQ?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">How to develop a vaccine, quickly.</span></figcaption>
</figure>
<h2>How protective does a vaccine need be to receive FDA approval?</h2>
<p>The FDA has set the bar for the primary endpoint of a Phase 3 trial of 50% protection for approval of a COVID-19 vaccine. </p>
<p>Protection is defined as protection from symptomatic COVID-19 infection, defined as laboratory-confirmed SARS-CoV-2 infection plus symptoms such as fever or chills, cough, shortness of breath, fatigue, muscle aches, loss of taste or smell, congestion or runny nose, diarrhea, nausea or vomiting. </p>
<p>This means that an effective vaccine is considered one that will reduce the number of infections in vaccine recipients by half. This is the <a href="https://doi.org/10.1016/S0140-6736(20)31821-3">minimal protection that is anticipated to be clinically useful</a>. That is, in part, because lower levels of efficacy could paradoxically increase COVID-19 infections if it leads vaccinated people to decrease mask wearing or social distancing because they think they are completely protected.</p>
<p>Since a vaccine might be more effective at preventing severe COVID-19, the FDA instructs that <a href="https://www.fda.gov/media/139638/download">protection from severe COVID-19</a> should be a secondary endpoint.</p>
<h2>How many people have to be vaccinated to know if a vaccine works in Phase 3?</h2>
<p>The current Phase 3 trials are enrolling 30,000-40,000 subjects. Most of these participants will receive the vaccine and some a placebo.</p>
<p>When, exactly, the results of Phase 3 studies will be released depends in large part on the rate of infection in the placebo recipients. The way that these vaccine studies work is that they test if naturally acquired new coronavirus infections are lower in the group that received the vaccine compared with the group receiving the placebo. </p>
<p>So while it is good news that COVID-19 infections have dropped recently in the U.S. from <a href="https://www.nytimes.com/interactive/2020/us/coronavirus-us-cases.html?auth=login-email&login=email">70,000 to 40,000 cases per day</a>, this drop in new infections may slow the vaccine studies.</p>
<h2>Will Emergency Use Authorization fast-track vaccine?</h2>
<p>In an emergency such as we are faced with the COVID-19 pandemic, with approximately 700 new deaths and 40,000 new cases per day right now, the FDA is authorized to allow the use of unapproved products for the diagnosis, treatment and prevention of disease. That includes a vaccine.</p>
<p><a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents/development-and-licensure-vaccines-prevent-covid-19">The standard approval process for vaccines</a> can require more than one year of observation after vaccination. If the short-term safety is good and the vaccine works to prevent COVID-19, then the vaccine should be approved for use under an Emergency Use Authorization while it is still being studied.</p>
<p>Under Emergency Use Authorization, the FDA will <a href="https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization">continue to collect information</a> from the companies producing the vaccines for benefit and harm, including surveillance for vaccine-associated enhanced respiratory disease or other potentially rare complications that might be observed in only one in a million.</p>
<h2>What should we expect in terms of approvals?</h2>
<p>I expect that the FDA will approve several vaccines by the end of 2020 under its Emergency Use Authorization authority so that vaccination can begin immediately, starting with high-risk groups including first responders, health care personnel, and the elderly and those with preexisting medical conditions. </p>
<p>This will be followed rapidly with <a href="https://theconversation.com/video-who-should-get-a-covid-19-vaccine-first-146285">roll-out of vaccination</a> to the population at large, while all of the time the FDA and vaccine manufacturers will continue to monitor for side effects and work to improve upon these first vaccines. This process is <a href="https://www.usatoday.com/story/news/health/2020/09/02/covid-19-vaccine-rollout-plan-united-states-worries-experts/5694037002/">expected to take months</a>.</p>
<p>It may not be life back to normal next year, but all signs point to a healthier 2021.</p>
<p><em>This article was updated on September 25 with information on the Johnson & Johnson vaccine trial.</em></p><img src="https://counter.theconversation.com/content/146091/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>William Petri receives funding from the NIH and the Bill & Melinda Gates Foundation.</span></em></p>Several vaccines are in Phase 3 trials. So when will we know whether any of these will protect against COVID-19?William Petri, Professor of Medicine, University of VirginiaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1460612020-09-21T13:38:41Z2020-09-21T13:38:41ZExplainer: How clinical trials test COVID-19 vaccines<figure><img src="https://images.theconversation.com/files/358513/original/file-20200917-14-1p5cq9j.jpg?ixlib=rb-1.1.0&rect=299%2C0%2C4693%2C3502&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A lab technician holds a vial of a COVID-19 vaccine candidate during testing at the Chula Vaccine Research Center, run by Chulalongkorn University in Bangkok, Thailand on May 25, 2020. </span> <span class="attribution"><span class="source">(AP Photo/Sakchai Lalit)</span></span></figcaption></figure><p>On Sept. 4, 2020, <a href="https://www.politico.com/news/2020/09/04/trump-coronavirus-vaccine-october-409248">President Donald Trump announced</a> that we will have a vaccine for COVID-19 “before the end of the year and maybe even before Nov. 1.” As an election looms in the United States, the declaration fuelled worry that a COVID-19 vaccine may be approved before scientific vetting is complete.</p>
<p>In the United States, review and licensure of vaccines is the responsibility of the Food and Drug Administration (FDA). But the agency’s handling of emergency use authorizations for <a href="https://www.statnews.com/2020/06/16/hydroxychloroquine-emergency-use-patients-politicians/">two anti-malaria drugs</a> and <a href="https://www.sciencemag.org/news/2020/08/fda-s-green-light-treating-covid-19-plasma-critics-see-thin-evidence-and-politics">convalescent blood plasma</a> for the treatment of COVID-19 have led to claims it has become <a href="https://www.citizen.org/news/blatant-politicization-of-the-fda-hurts-its-credibility/">politicized</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/358514/original/file-20200917-14-33bn21.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A purple-gloved hand is selecting one of nine vials of blood in a green stand." src="https://images.theconversation.com/files/358514/original/file-20200917-14-33bn21.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/358514/original/file-20200917-14-33bn21.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=402&fit=crop&dpr=1 600w, https://images.theconversation.com/files/358514/original/file-20200917-14-33bn21.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=402&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/358514/original/file-20200917-14-33bn21.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=402&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/358514/original/file-20200917-14-33bn21.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=505&fit=crop&dpr=1 754w, https://images.theconversation.com/files/358514/original/file-20200917-14-33bn21.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=505&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/358514/original/file-20200917-14-33bn21.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=505&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Blood samples from volunteers are handled in the laboratory at Imperial College in London, on July 30, 2020. Imperial College is working on the development of a COVID-19 vaccine.</span>
<span class="attribution"><span class="source">(AP Photo/Kirsty Wigglesworth)</span></span>
</figcaption>
</figure>
<p>Such is the worry about the impartiality of the FDA that <a href="https://www.statnews.com/pharmalot/2020/09/07/pharma-covid-19-vaccine-drew-a-line/">pharmaceutical companies drew a line in the sand</a> and <a href="https://www.pfizer.com/news/press-release/press-release-detail/biopharma-leaders-unite-stand-science">pledged publicly</a> to “only submit [a vaccine] for approval or emergency use authorization after demonstrating safety and efficacy through a Phase 3 clinical study.”</p>
<p>“Hell has frozen over,” <a href="https://www.statnews.com/2020/09/10/hell-has-frozen-over-pharmaceutical-industry-stands-in-for-politically-impaired-fda/">remarked commentators</a>.</p>
<p>But what is a Phase 3 clinical study? And how does scientific testing provide us with reliable evidence that vaccines not only work but are safe?</p>
<h2>Vaccine development</h2>
<p><a href="https://www.historyofvaccines.org/content/articles/vaccine-development-testing-and-regulation">Vaccine development</a> can be thought of as the process of separating the parts of an infectious agent that make us sick, from those that induce an immune response and protect us from future infection. As this separation can be accomplished in myriad ways, vaccines are diverse. </p>
<p>Vaccine candidates for COVID-19 <a href="https://doi.org/10.1038/d41586-020-01221-y">illustrate these diverse approaches</a>. Some, such as <a href="https://blogs.sciencemag.org/pipeline/archives/2020/08/17/sinopharms-inactivated-coronavirus-vaccine">SinoPharm’s inactivated coronavirus vaccine</a>, use killed whole coronavirus. Others, such as the <a href="https://www.statnews.com/2020/07/20/study-provides-first-glimpse-of-efficacy-of-oxford-astrazeneca-covid-19-vaccine/">Oxford University-AstraZeneca vaccine</a>, modify a different virus (in this case, chimpanzee adenovirus) to express coronavirus proteins. Yet others, such as <a href="https://www.nationalgeographic.com/science/2020/05/moderna-coronavirus-vaccine-how-it-works-cvd/#:%7E:text=The%20surface%20of%20the%20SARS,it%20can%20establish%20an%20infection.">Moderna’s mRNA vaccine</a>, use only small bits of viral genetic material. </p>
<p>In Canada, the <a href="https://www.canada.ca/en/health-canada/services/drugs-health-products/biologics-radiopharmaceuticals-genetic-therapies/activities/fact-sheets/regulation-vaccines-human-canada.html">oversight of vaccines</a> is shared by <a href="https://www.canada.ca/en/health-canada.html">Health Canada</a> and the <a href="https://www.canada.ca/en/public-health.html">Public Health Agency of Canada</a>. The <a href="https://www.cdc.gov/vaccines/basics/test-approve.html">scientific evaluation of vaccines</a> involves animal testing, human clinical trials and post-approval surveillance. In many regards, the evaluation of vaccines is the same as the process for drugs. Because vaccines are given to healthy people, however, there is an even greater emphasis in vaccine testing on safety. </p>
<h2>Animal testing</h2>
<p>The first step in evaluating a vaccine is animal testing. Animals are given differing doses of vaccine to check for adverse events and an immune response. </p>
<p>As the virus that causes COVID-19 is new, there was no animal model for the disease. <a href="https://doi.org/10.1126/science.abc6141">Recent work</a> has demonstrated that ferrets, cats and some non-human primates are prone to infection and can spread it to others. Animal testing provides information about safety (and perhaps efficacy) before a vaccine is tested on humans.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/74WQgNa3OsQ?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">What is vaccine development, and how can it be done faster during a pandemic?</span></figcaption>
</figure>
<h2>Human clinical trials</h2>
<p><a href="https://dx.doi.org/10.4103%2F0022-3859.173187">Human testing in clinical trials</a> is divided into three phases. Ensuring the safety of a vaccine is the prime concern through all phases of clinical trials. Vaccine efficacy is evaluated in different ways across the trial spectrum. Early-phase trials look for the production of antibodies against the virus, while late-phase trials evaluate whether the vaccine in fact prevents people from getting sick.</p>
<p>Phase 1 trials are the first evaluations of a vaccine in humans. These trials recruit 10 to 100 healthy volunteers who receive different doses of vaccine. Common adverse events to a vaccine include redness or soreness at the injection site, muscle pains, headache and fever. Blood is also drawn from the volunteers to assess the immune response to the vaccine, particularly the rise in antibodies and whether antibody levels are similar to those in people who have had the disease.</p>
<p>Phase 2 vaccine trials are similar to Phase 1 trials in terms of their focus on adverse events and immune response. Phase 2 trials, however, include hundreds of healthy volunteers who are more diverse to give a better indication of the safety and immune response in people likely to receive the vaccine in the future. </p>
<figure class="align-center ">
<img alt="A woman with her back to the camera sits on the examination table in an examination room as a man in a white coat and purple gloves gives her an injection in her upper left arm." src="https://images.theconversation.com/files/358515/original/file-20200917-18-1dkygf9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/358515/original/file-20200917-18-1dkygf9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/358515/original/file-20200917-18-1dkygf9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/358515/original/file-20200917-18-1dkygf9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/358515/original/file-20200917-18-1dkygf9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/358515/original/file-20200917-18-1dkygf9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/358515/original/file-20200917-18-1dkygf9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Pharmacist Michael Witte, left, gives Rebecca Sirull, right, a shot in the first-stage safety study clinical trial of a potential vaccine for COVID-19 on March 16, 2020, at the Kaiser Permanente Washington Health Research Institute in Seattle. Sirull was the third patient to receive the shot in the study.</span>
<span class="attribution"><span class="source">(AP Photo/Ted S. Warren)</span></span>
</figcaption>
</figure>
<p>As Phase 1 and 2 trials involve relatively small numbers of people, they only give us information on vaccine side-effects that are very common (affecting more than 10 per cent of people) and common (affecting more than one per cent of people). Vaccine efficacy is only evaluated indirectly through measuring antibody levels.</p>
<p>It is only the Phase 3 trials that can provide a pivotal demonstration that a vaccine both works and is safe. Phase 3 vaccine trials are large randomized controlled trials conducted in the community. In these trials people either receive the vaccine or a placebo. If fewer people who received the vaccine become sick compared to those who received placebo, we have direct evidence that the vaccine prevents disease.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/ethics-must-not-be-ignored-when-testing-covid-19-vaccines-141736">Ethics must not be ignored when testing COVID-19 vaccines</a>
</strong>
</em>
</p>
<hr>
<p>A Phase 3 trial may involve tens of thousands of volunteers who receive the vaccine, further providing reliable information on adverse events, including those that are uncommon (affecting fewer than one per cent of people) or rare (affecting fewer than 0.1 per cent of people).</p>
<p>A vaccine may be licensed for use after a successful Phase 3 trial.</p>
<p>Of the 321 <a href="https://cepi.net/news_cepi/321-vaccine-candidates-against-covid-19-now-in-development/">vaccines for COVID-19 in development</a>, 27 are in Phase 1 or 2 trials and six are being evaluated in Phase 3 trials. In total, these trials seek to enrol 280,000 people from 34 countries. No COVID-19 vaccine has been licensed in Canada or the United States. </p>
<h2>Post-approval surveillance</h2>
<p>Once a vaccine is licensed, continued monitoring for safety is critical. Reliable detection of very rare (affecting fewer than 0.01 per cent of people) vaccine adverse events requires information on hundreds of thousands of people. The <a href="https://www.canada.ca/en/public-health/services/immunization/canadian-adverse-events-following-immunization-surveillance-system-caefiss.html">Canadian Adverse Events Following Immunization Surveillance System</a> monitors the safety of marketed vaccines, publishes reports regularly and identifies the need for further study should a safety issue be identified.</p>
<p>Provided that a COVID-19 vaccine successfully navigates human clinical trials and is subjected to continuing safety monitoring after it is licensed, we have good grounds to believe that the vaccine both works and is safe.</p><img src="https://counter.theconversation.com/content/146061/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Charles Weijer consults with Cardialen, Eli Lilly & Company, and Research Triangle Institute (RTI) International.</span></em></p>Will a vaccine for COVID-19 be safe? Animal testing, human clinical trials and post-approval surveillance give us good grounds to believe that a future approved vaccine will work and be safe.Charles Weijer, Professor of medicine, epidemiology & biostatistics, and philosophy, Western UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1454722020-09-02T14:58:25Z2020-09-02T14:58:25ZPasha 79: Why South Africa’s role in COVID-19 vaccine trials is important<figure><img src="https://images.theconversation.com/files/356035/original/file-20200902-18-1rgmn2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">shutterstock</span> </figcaption></figure><p>South Africa is one of the countries where trials are under way to find an efficacious vaccine against SARS-CoV-2, the virus that causes COVID-19 disease. South Africa’s participation in these trials is crucial. These vaccines are produced in the West and it’s important that they prove to be safe and effective in African countries. Participation in the trials also means that should a vaccine prove to work, the country may have easier access to it.</p>
<p>In today’s episode of Pasha, Professor Linda-Gail Bekker and Professor Keertan Dheda at the University of Cape Town discuss why vaccine trials are important and why South Africa needs to be involved. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/pasha-78-south-africas-second-covid-19-vaccine-trial-explained-145113">Pasha 78: South Africa's second COVID-19 vaccine trial explained</a>
</strong>
</em>
</p>
<hr>
<p><strong>Photo:</strong>
“Corona Virus Vaccine Trial - Covid 19 or Corona Virus human clinical trials vaccination shot or injection shot.” By dkroy <a href="https://www.shutterstock.com/image-photo/corona-virus-vaccine-trial-covid-19-1772604524">Shutterstock</a></p>
<p><strong>Music</strong>
“Happy African Village” by John Bartmann, found on <a href="http://freemusicarchive.org/music/John_Bartmann/Public_Domain_Soundtrack_Music_Album_One/happy-african-village">FreeMusicArchive.org</a> licensed under <a href="https://creativecommons.org/publicdomain/zero/1.0/">CC0 1</a>.</p>
<p>“Together We Stand” by Scott Holmes, found on <a href="https://freemusicarchive.org/music/Scott_Holmes/Cinematic_Background_Music/-_Together_We_Stand">FreeMusicArchive.org</a> licensed under <a href="http://creativecommons.org/licenses/by-nc/4.0/">Attribution-NonCommercial License.</a>.</p><img src="https://counter.theconversation.com/content/145472/count.gif" alt="The Conversation" width="1" height="1" />
The vaccines being tested in South Africa have been included on the World Health Organization’s list of 26 most viable candidate vaccines to enter human clinical trials.Ozayr Patel, Digital EditorLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1417362020-08-24T15:29:28Z2020-08-24T15:29:28ZEthics must not be ignored when testing COVID-19 vaccines<figure><img src="https://images.theconversation.com/files/354173/original/file-20200821-14-oybbsh.jpg?ixlib=rb-1.1.0&rect=0%2C17%2C5961%2C2529&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">As human trials begin for potential COVID-19 vaccines, the ethics of human challenges studies must be considered.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>The grassroots organization 1Day Sooner has been <a href="https://www.newsweek.com/coronavirus-covid-19-1-day-sooner-volunteers-infected-vaccine-human-challenge-trial-1500030">asking people to indicate their willingness to volunteer for human challenge studies of COVID-19</a>. Challenge studies, in which healthy people are intentionally exposed to infection, may, they believe, speed vaccine development. </p>
<p>1Day Sooner reports that <a href="https://1daysooner.org/">more than 35,000 people from 160 countries, including Canada, are ready to volunteer to be exposed to COVID-19</a>. </p>
<p>But should we let them? </p>
<p>Many find the idea of <a href="https://www.sciencemag.org/news/2016/05/studies-intentionally-infect-people-disease-causing-bugs-are-rise">human challenge studies</a> surprising. Why would scientists want to expose healthy volunteers to an infectious disease? One reason is to efficiently conduct a preliminary test of a new vaccine. </p>
<p>In a vaccine challenge study, participants are given either a new vaccine or a placebo and then deliberately exposed to the infectious agent. If fewer people who were given the vaccine become ill compared to the placebo group, we have preliminary evidence the vaccine works. </p>
<p>Challenge studies stand traditional clinical trials on their head. In a clinical trial, the patient receives a novel treatment that may improve her medical condition. There are risks from experimental treatment, but those risks are offset by the prospect of direct benefit to the patient. </p>
<p>Challenge studies, by contrast, deliberately seek to make healthy volunteers sick and offer no prospect of direct benefit. Because challenge studies do not benefit volunteers, we limit the risk to which they may be exposed for scientific ends.</p>
<h2>Ethical research</h2>
<p>Can we ethically conduct a vaccine challenge study involving COVID-19? According to <a href="https://doi.org/10.1093/phe/phv026">current ethical guidelines</a>, published in 2016 and on which I served as co-author, the ethical permissibility of challenge studies entails a range of requirements, including a compelling scientific rationale, minimization of risks to participants and detailed informed consent ethical guidelines for human challenge studies.</p>
<p>A key provision requires that “volunteers will under no circumstances be exposed to the risks of irreversible, incurable or possibly fatal infections.” And while <a href="https://www.sciencemag.org/news/2016/05/studies-intentionally-infect-people-disease-causing-bugs-are-rise#">challenge studies were used to develop vaccines for cholera and malaria</a>, this research was permissible because there are drugs that reliably cure both illnesses. </p>
<p>But the proposal to conduct challenge studies of COVID-19 fails to satisfy this key ethical requirement. The <a href="https://health-infobase.canada.ca/covid-19/epidemiological-summary-covid-19-cases.html">mortality rate for COVID-19 in Canada is 7.3 per cent</a>. Even if challenge studies were restricted to adults in their 20s, the <a href="https://doi.org/10.1016/S1473-3099(20)30243-7">risk of death is 0.03 per cent, or about one in 3,000 patients</a>. </p>
<p>While the primary impact of COVID-19 appears to be on the lungs, it is now clear that the <a href="https://www.sciencemag.org/news/2020/04/how-does-coronavirus-kill-clinicians-trace-ferocious-rampage-through-body-brain-toes">disease affects many organs</a>, leaving some patients with lasting disabilities. As yet, there is no curative treatment for COVID-19. </p>
<h2>Challenging ethics</h2>
<p>Researchers have argued that we ought to <a href="https://doi.org/10.1093/infdis/jiaa152">change widely accepted ethical standards to allow COVID-19 challenge studies</a>, claiming that challenge studies could greatly speed the development of a COVID-19 vaccine and, as a consequence, “the savings in human lives could be in the thousands or conceivably millions.” </p>
<p>In a recent <a href="https://www.ted.com/talks/nir_eyal_the_case_to_infect_volunteers_with_covid_19_to_accelerate_vaccine_testing/reading-list?referrer=playlist-itunes_podcasts_science_medicine&language=en#t-611647">TED talk</a>, bioethicist Nir Eyal claims that the threshold for permissible risk in challenge studies is too low. We allow adults to donate a kidney to a person in need of a transplant even though this involves a risk of death of one in 3,000 to the donor. </p>
<p>Why not allow healthy volunteers to agree to similar risks in a COVID-19 challenge study? </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/3jWsc0cG0wI?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Bioethicist Nir Eyal argues that the risks to a healthy person of dying from COVID-19 are similar to the risks of donating a kidney.</span></figcaption>
</figure>
<h2>Moving forward safely</h2>
<p>Neither of these arguments is compelling. There are reasons to doubt that COVID-19 challenge studies would in fact give us a vaccine sooner. One or two years of development is typically required before a challenge study with a new infectious agent can proceed. For COVID-19, <a href="http://doi.org/10.1056/NEJMp2020076">scientists would need to standardize the viral strain</a> and determine a dose that reproducibly causes mild disease but does not cause severe disease. </p>
<p>Meanwhile, standard avenues of vaccine research and development are proceeding quickly. More than <a href="https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines">160 vaccine candidates have been identified</a>, of which 30 are now being tested in human clinical trials. Two vaccine trials are <a href="http://doi.org/10.1038/d41586-020-02174-y">enrolling thousands of volunteers in Brazil, South Africa, the United Kingdom and the United States</a>. </p>
<p>Philip Dormitzer, chief scientific officer at Pfizer Vaccines Research and Development recently commented: “<a href="http://doi.org/10.1001/jama.2020.9881">I think we can probably be faster by taking these vaccines forward and testing them in a conventional way</a>.” </p>
<h2>Preserving trust</h2>
<p>What of the claim that the threshold for permissible risk in challenge studies is too low? Here the argument relies on an analogy between donating a kidney and participating in a vaccine challenge study. This assumes the two cases are comparable; they are not. </p>
<p>Decades of experience in kidney transplantation means the <a href="http://doi.org/10.1053/j.ackd.2011.09.005">risks to donors are well understood</a>. Our experience with COVID-19 is all too brief, and little information is available on the long-term consequences of infection. </p>
<p>Further, a kidney transplant from a closely matched donor has high probability of success. The benefits of a vaccine challenge study are far less likely, since (based on experience with other diseases) only a minority of vaccine candidates will ultimately be licensed for use. </p>
<p>Over the last 50 years, <a href="https://doi.org/10.1111/tmi.13320">thousands of people have volunteered for challenge studies</a>. Participants have endured the diarrhea caused by cholera and malarial fevers, but none have died. This is a testament to the skill and extraordinary efforts of scientists to protect volunteers. In drawing the line at “risks of irreversible, incurable or possibly fatal infections,” scientists seek not only to protect volunteers but also preserve the public’s trust in the scientific enterprise. </p>
<p>If ethical standards are lowered and COVID-19 challenge studies are allowed to proceed, my fear is that volunteers will suffer irreparable harm and die. This runs the risk of undermining public trust in both research and vaccines. Public trust is now — and will remain — an indispensable element in our efforts to defeat COVID-19.</p><img src="https://counter.theconversation.com/content/141736/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Charles Weijer consults with Cardialen, Eli Lilly & Company, and Research Triangle Institute (RTI) International.</span></em></p>Thousands of people around the world have said they are willing to be exposed to COVID-19 to test new vaccines. Since we don’t fully understand the long-term effects of the disease, is this ethical?Charles Weijer, Professor of medicine, epidemiology & biostatistics, and philosophy, Western UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1442402020-08-17T12:24:24Z2020-08-17T12:24:24ZThe ethical case for allowing medical trials that deliberately infect humans with COVID-19<figure><img src="https://images.theconversation.com/files/353054/original/file-20200816-14-oc0umk.jpg?ixlib=rb-1.1.0&rect=6%2C0%2C2233%2C1491&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Could intentionally infecting volunteers in COVID-19 trials speed up a vaccine?</span> <span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Virus-Outbreak-Vaccine-Study/92a3ec84082449ab8cd8c52ae3aa86dd/102/0">AP Photo/Ted S. Warren</a></span></figcaption></figure><p>Despite the urgent need to beat COVID-19, health officials may be delaying the development of an effective vaccine.</p>
<p>Authorities in the U.S. and elsewhere are yet to authorize an ethically charged research procedure called “<a href="https://www.sciencemag.org/news/2020/07/controversial-human-challenge-trials-covid-19-vaccines-gain-support">human challenge trials</a>.” Challenge trials entail deliberately infecting volunteers with the disease – which explains the official reticence – but they could substantially expedite the development of a vaccine.</p>
<p>The debate over human challenge trials has been <a href="https://www.tandfonline.com/doi/full/10.1080/15265161.2020.1779393">raging for months</a> among health professionals and academics. But only now – some eight months into the pandemic – are <a href="https://www.washingtonpost.com/health/2020/08/14/us-will-prepare-coronavirus-strain-potential-human-challenge-trials/">authorities in the U.S. beginning to consider</a> them in a bid to speed up the vaccine-development process.</p>
<h2>Sitting and waiting</h2>
<p>A vaccine has to <a href="https://www.cdc.gov/vaccines/basics/test-approve.html">go through multiple stages</a> before it can be rolled out. After establishing its ability to trigger an immune response and its safety, developers must test it for efficacy. Inefficient vaccines may not justify the tiny risk inherent even in safe vaccines, may be enormously wasteful, may divert resources from better alternatives and may harm immunization rates.</p>
<p>There are two principal ways with which to measure efficacy. Under the conventional method, researchers vaccinate tens of thousands of volunteers and then passively wait for some of them to get infected. The frequency of infection is then compared to a non-vaccinated control group.</p>
<p>In the second method, human challenge trials, a much smaller group of volunteers is intentionally infected after receiving the experimental vaccine or a placebo. This allows for a much faster and efficient determination of vaccine efficacy.</p>
<p>To date, <a href="https://1daysooner.org/">more than 33,000 people from 151 countries</a> have volunteered to be part of such a procedure. But there is no official authorization for human challenge trials for COVID-19 in the U.S. or other Western countries. This means that vaccine developers are forced to vaccinate many more volunteers – <a href="https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html">typically about 30,000 are involved</a> for each candidate vaccine – and then release them into the general population, with the hope that enough data would soon accumulate.</p>
<p>This is <a href="https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html">where we presently are in the U.S.</a>: waiting for enough participating volunteers to catch the virus by happenstance. </p>
<p>Paradoxically, these giant and expensive studies – American taxpayers have already spent <a href="https://www.usatoday.com/story/news/health/2020/08/08/feds-spending-more-than-9-billion-covid-19-vaccine-candidates/5575206002/">billions of dollars on vaccine development</a> – are slowed down by government efforts to minimize infection rates through quarantines, closures, masks usage or social distancing. Back in May, leading developers of potential COVID-19 vaccines, including the biotechnology company Moderna and Oxford University, <a href="https://www.washingtonpost.com/world/europe/coronavirus-vaccine-trials-astrazeneca-moderna/2020/06/09/48f28fea-a414-11ea-898e-b21b9a83f792_story.html?outputType=amp">issued a warning</a> that low-level infections among their volunteers may delay the development of their vaccines.</p>
<p>It is possible, of course, that the conventional studies will <a href="https://www.nih.gov/news-events/news-releases/phase-3-clinical-trial-investigational-vaccine-covid-19-begins">yield the required data</a>. But there is a distinct possibility that challenge trials could speed up things. </p>
<h2>Medical ethics</h2>
<p>Opposition to human challenge studies for COVID-19 is based, first and foremost, <a href="https://www.statnews.com/2020/06/23/challenge-trials-live-coronavirus-speedy-covid-19-vaccine/">on ethical considerations</a>. Since at present there is no cure for COVID-19, intentional infection can result in death or serious impairments. It is therefore <a href="https://www.statnews.com/2020/06/23/challenge-trials-live-coronavirus-speedy-covid-19-vaccine/">argued by people like Michael Rosenblatt</a>, a former dean of Tufts University School of Medicine and a present adviser to Moderna, that the risks are too high, and that volunteers cannot give a valid “informed consent” for intentional infection.</p>
<p>The argument that willing adults cannot consent to risking their health for the greater good is, we believe, inconsistent with how society views other acts of volunteerism. Volunteer firefighters, for example, also face unknown dangers. Moreover, few countries refrain from risking the health and lives of their young citizens on the world’s battlefields, if they deem that the common good requires such sacrifice. And while COVID-19 human challenge trials would include only volunteers, most battlefields also include people who are forced into service.</p>
<p>Delaying a vaccine may also endanger volunteering health care workers. Current estimates put the number of U.S. health care workers’ deaths from COVID-19 <a href="https://www.theguardian.com/us-news/ng-interactive/2020/aug/11/lost-on-the-frontline-covid-19-coronavirus-us-healthcare-workers-deaths-database">at around 1,000</a>. Health care volunteers continue risking their lives as long as vaccine development is delayed.</p>
<p>The opposition to human challenge trials derives from justified sensitivity to medical experiments on humans, and the horrific history of such experiments – which often ignored the interests and rights of their subjects. These included <a href="https://www.nytimes.com/2020/01/28/books/review/mengele-david-g-marwell.html">the experiments performed by the Nazis</a> on prisoners or the <a href="https://www.cdc.gov/tuskegee/timeline.htm">notorious Tuskegee Study</a> of untreated syphilis, which was conducted on unsuspecting African Americans. And of course, even medical experiments that subjects consent to <a href="https://www.bbc.com/news/magazine-35766627">can go terribly wrong</a>. </p>
<h2>Lives at stake</h2>
<p>But rapid development of an effective vaccine could save hundreds of thousands of lives worldwide. At present, more than <a href="https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200814-covid-19-sitrep-207.pdf?sfvrsn=2f2154e6_2">5,000 people die of COVID-19 each day</a>. At that rate, every month of delay in vaccine availability costs 150,000 lives. </p>
<p>The indirect costs are tremendous as well. For example, the United Nations recently announced that pandemic-linked hunger is tied to <a href="https://apnews.com/5cbee9693c52728a3808f4e7b4965cbd">10,000 child deaths each month</a>. From these perspectives, the arguments against human challenge trials appear far less convincing.</p>
<p>[<em>Deep knowledge, daily.</em> <a href="https://theconversation.com/us/newsletters/the-daily-3?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=deepknowledge">Sign up for The Conversation’s newsletter</a>.]</p>
<p>We believe that the decision to allow human challenge trials for COVID-19 should not be examined solely through the narrow lens of medical ethics – with its cardinal principal of doing no harm to the individual patient or the volunteer. The COVID-19 epidemic is a global disaster, and decisions concerning it should be made with the wider perspectives of public health and general morality. In other words, the decision may be more suitable for high level policymakers than for medical ethics committees.</p>
<p>In April, <a href="https://www.sciencemag.org/news/2020/04/united-states-should-allow-volunteers-be-infected-coronavirus-test-vaccines-lawmakers">some American lawmakers did weigh in</a>: 35 members of the U.S. House of Representatives sent a letter to the heads of the U.S. Food and Drug Administration and the Department of Health and Human Services, voicing support for human challenge trials. So far, however, this effort has had no effect.</p>
<p>There is no doubt that human challenge trials carry significant risks for volunteers; but they also carry the chance of significant benefits for humanity. Instead of regarding these volunteers as uninformed, society may do better to valorize their altruism and heroism. We believe that, given present circumstances, human challenge trials for COVID-19 are not morally wrong: To the contrary, they express humanity’s most noble values.</p><img src="https://counter.theconversation.com/content/144240/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Conventional trials to test coronavirus vaccines are paradoxically slowed down by actions to curb the disease’s spread. Human challenge trials are more controversial, but could speed up the process.Ofer Raban, Professor of Constitutional Law, University of OregonYuval Dor, Professor of Biology, Hebrew University of JerusalemLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1423052020-07-08T13:26:57Z2020-07-08T13:26:57ZCOVID-19 vaccine trial in South Africa: everything you need to know<figure><img src="https://images.theconversation.com/files/346352/original/file-20200708-23-1oz59lw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A general view during the country's first human clinical trial for a potential COVID-19 vaccine in Soweto, South Africa. </span> <span class="attribution"><span class="source">Felix Dlangamandla/Beeld/Gallo Images via Getty Images</span></span></figcaption></figure><p><em>There isn’t enough clinical research being done in Africa. Less than <a href="https://theconversation.com/africa-hosts-very-few-clinical-trials-why-this-is-bad-for-innovation-97390">2.5% of all clinical trials</a> in the world are done on the continent. This is why South Africa’s <a href="http://www.wits.ac.za/covid19vaccine/">involvement in one of the COVID-19 vaccine trials</a> is so important. The country’s effort is being led by Professor Shabir Madhi. The Conversation Africa’s health and medicine editor Ina Skosana spoke to him about the process, and what can be expected. This is an edited version of a podcast, which you can listen to <a href="https://theconversation.com/pasha-71-covid-19-vaccine-trial-in-south-africa-explained-142303">here</a>.</em></p>
<hr>
<h2>How does the trial work?</h2>
<p>The study that we embarked on in South Africa is for a vaccine that was developed by the Jenner Institute at the University of Oxford. It’s what is known as a non-replicating vector base COVID-19 vaccine. </p>
<p>The study came about when I reached out to the principal investigator at the University of Oxford whom I’ve known for over 20 years to find out if there was any interest on their part to include South Africa as part of the clinical development plan of the vaccine. The short answer was yes, provided we conducted the study on our own, including raising the funding to conduct the study. </p>
<p>The agreement with Oxford University preceded a subsequent agreement that they’ve entered into with <a href="https://www.astrazeneca.com/">AstraZeneca</a>, the pharmaceutical company responsible for the further clinical development of the vaccine and future manufacturing. Pre-clinical studies of this vaccine candidate, including in non-human primates, have demonstrated initial evidence of the safety of this vaccine, as well as its ability to protect against COVID-19 disease.</p>
<h2>Why South Africa?</h2>
<p>The main reason is that the legacy of vaccines shows that they don’t necessarily work similarly across different populations. So if we want to be one of the early adopters, in terms of implementing vaccination against COVID-19 as part of our immunisation programme, we really need to generate data applicable to the local context. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/africa-must-make-sure-its-part-of-the-search-for-a-coronavirus-vaccine-136531">Africa must make sure it's part of the search for a coronavirus vaccine</a>
</strong>
</em>
</p>
<hr>
<p>A number of past vaccines have been shown to be highly efficacious in high income settings. But when they’ve gone on to be evaluated in low and middle income settings, they were found to be much less efficacious and, at times, not efficacious at all. </p>
<p>So if we want to make informed decisions at an early stage about whether these vaccines are going to be of benefit to people in South Africa, it’s critical that we undertake the clinical evaluation during the start of the entire programme, rather than at the latter stage. Waiting for results to come in from other studies would just lead to a lag in terms of the timing when vaccines would be introduced in South Africa as well as other low and middle income countries. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/africa-waited-for-solutions-to-past-health-crises-will-it-be-different-for-covid-19-140984">Africa waited for solutions to past health crises: will it be different for COVID-19?</a>
</strong>
</em>
</p>
<hr>
<p>This has been the experience for many other life saving vaccines where it has taken between five and 20 years between their availability in high income countries and low middle income countries.</p>
<h2>How are participants chosen for the trial?</h2>
<p>Participation is completely voluntary. </p>
<p>Participants typically come to inquire about the study at clinics. We sit down with them and explain what the study is all about. What are the criteria for joining, what the expectations are of the volunteers because the study has quite intense expectations in terms of being able to come for regular visits. And they obviously need to be agreeable that when they do participate in the study, if they do develop signs and symptoms suggestive of COVID-19, that they would come forward to be investigated. This is critical for us to be able to determine whether this vaccine protects against COVID-19. </p>
<p>In addition, we would do some blood tests which ensures that they don’t have any sort of medical conditions that we would want to exclude. </p>
<p>If they’re found to be eligible, we randomly allocate them to one of two groups. Half will receive the vaccine, and the other half a control substance, which in our case, is a placebo. This is important for two reasons. The first is that it allows us to provide robust data in terms of the safety profile of the vaccine. And the control group enables us to determine whether the vaccine actually does have any impact in protecting against COVID-19.</p>
<h2>Is there any reason people should be sceptical of the trial?</h2>
<p>The short answer is no. The narratives that Africans are being used as guinea pigs is fundamentally incorrect. Rather a case of us wanting to generate robust scientific data to be able to make informed decisions about whether those vaccines actually do protect South Africans – and possibly Africans more generally – against developing COVID-19.</p>
<h2>What are the next steps?</h2>
<p>Right now we busy enrolling into the clinical trial. We’ve just reached the 200 mark out of the 2000 participants that we plan to enrol. We expect to have completed enrollment of all the volunteers over the next three to four weeks. </p>
<p>After that we will keep in touch with all of the participants at least every two weeks, including weekly SMS messages to determine whether or not experiencing any signs or symptoms of COVID-19. And if they are they will be asked to come in to be investigated to determine whether they are infected or not. </p>
<p>The endgame of the study is twofold. One is obviously to evaluate the safety of the vaccine, which is something that is ongoing almost on a daily basis. </p>
<p>The second part is that once we have about 42 individuals that have developed COVID-19 at least about a month after they’ve received the first dose of either the vaccine or the placebo we will then be able to do an analysis to determine whether the vaccine actually does protect against COVID-19. Specifically we will be testing if the vaccine efficacy is at least 60%; that is by being vaccinated your risk for developing COVID-19 will be reduced by at least 60% if not more. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/covid-19-vaccine-the-challenges-of-running-a-trial-in-the-middle-of-a-pandemic-141728">COVID-19 vaccine: the challenges of running a trial in the middle of a pandemic</a>
</strong>
</em>
</p>
<hr>
<p>We anticipate that we will probably be able to provide an answer as to whether this vaccine works and protects against COVID-19 by the end of November this year. In the worst case scenario it might take us a bit longer probably into the second quarter of next year. </p>
<h2>What about managing expectations?</h2>
<p>It’s very exciting to be involved in the sort of clinical development of the vaccine. But we need to be guarded in terms of our expectations as to what the result will be. </p>
<p>The fact that we’re embarking on a clinical trial doesn’t mean that we’re going to have a vaccine that’s going to protect against COVID-19. </p>
<p>Only about <a href="https://www.nytimes.com/interactive/2020/04/30/opinion/coronavirus-covid-vaccine.html">10% of vaccines</a> that go into clinical trials are eventually licensed for use. Right now there’ are approximately <a href="https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines">200 vaccines</a> that are being developed for COVID-19. It would be a huge accomplishment if, over the next 12 to 18 months, we are successful showing that even one out of every 20 (5%) of the vaccines that go into human studies are safe and provide some protection against COVID-19. </p>
<p>So even though there’s a huge amount of work taking place around vaccines, at least for the next 12 months the only tools that we’ve got available to us to try to protect people is adherence to physical distancing, the wearing of face masks in public spaces, avoiding mass gatherings, and making sure that you’re in adequately ventilated settings when in public spaces. </p>
<p><em>Anyone living in South Africa who is interested in participating in the study can e-mail vidacov19@rmpru.co.za for more information.</em></p><img src="https://counter.theconversation.com/content/142305/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Shabir Madhi's institution (Wits Health Consortium, a subsidiary of The University of the Witwatersrand) is receiving funding from the South African Medical Research Council and The Bill & Melinda Gates Foundation to conduct the COVID-19 vaccine study in South Africa. Neither of the funders are involved in the actual conduct of the study. </span></em></p>There isn’t enough clinical research being done in Africa. This has had a lot of repercussions in terms of the timing when interventions become available and effective in high income countries.Shabir A. Madhi, Professor of Vaccinology and Director of the SAMRC Vaccines and Infectious Diseases Analytical Research Unit, University of the WitwatersrandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1396662020-06-03T05:56:20Z2020-06-03T05:56:20ZThe fascinating history of clinical trials<figure><img src="https://images.theconversation.com/files/339370/original/file-20200603-133919-3y3xtd.JPG?ixlib=rb-1.1.0&rect=3%2C3%2C1149%2C809&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://wellcomecollection.org/works/brpzukyc">Wellcome Collection</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>Clinical trials are under way around the world, including in Australia, testing <a href="https://www.mja.com.au/journal/2020/clinical-trials-prevention-and-treatment-coronavirus-disease-2019-covid-19-current">COVID-19 vaccines and treatments</a>.</p>
<p>These <a href="https://www.bmj.com/about-bmj/resources-readers/publications/epidemiology-uninitiated/">clinical trials</a> largely fall into two groups. With <a href="https://www.ctu.mrc.ac.uk/patients-public/about-clinical-trials/what-is-an-observational-study/">observational studies</a>, researchers follow a group of people to see what happens to them. With <a href="https://www.bmj.com/about-bmj/resources-readers/publications/epidemiology-uninitiated/9-experimental-studies">experimental studies</a>, people are assigned to treatments, then followed. </p>
<p>These study designs have come about from centuries of people trying out different ways of treating people.</p>
<p>Here are some of the key moments in the history of clinical trials that led to the type of trials we see today for COVID-19.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/from-the-research-lab-to-your-doctors-office-heres-what-happens-in-phase-1-2-3-drug-trials-138197">From the research lab to your doctor's office – here's what happens in phase 1, 2, 3 drug trials</a>
</strong>
</em>
</p>
<hr>
<h2>Ginseng in 11th-century China</h2>
<p>One of the earliest observational studies occurred nearly 1,000 years ago in China. The 1061 <a href="https://www.jameslindlibrary.org/ben-cao-tu-jing-11th-century/">Atlas of Materia Medica</a> (Ben Cao Tu Jing) was compiled and edited by <a href="https://en.wikipedia.org/wiki/Su_Song">Song Su</a>, a renowned scientist, administrator, diplomat and military strategist.</p>
<p>It <a href="https://books.google.com.au/books?id=G7uXK9Z2TSoC&pg=PA47&lpg=PA47&dq=to+evaluate+the+effect+of+genuine+Shangdang+ginseng,+two+persons+were+asked+to+run+together.+One+was+given+the+ginseng+while+the+other+ran+without.+After+running+for+approximately+three+to+five+li+%5Babout+1500+to+2500+metres%5D,+the+one+without+the+ginseng+de&source=bl&ots=eJSCJQEIrQ&sig=ACfU3U3YI_8OIFINP28Xg4cOgAMaJ4W7rA&hl=en&sa=X&ved=2ahUKEwjP9MnNs-TpAhUMOisKHZvuB4MQ6AEwAHoECAoQAQ#v=onepage&q=to%20evaluate%20the%20effect%20of%20genuine%20Shangdang%20ginseng%2C%20two%20persons%20were%20asked%20to%20run%20together.%20One%20was%20given%20the%20ginseng%20while%20the%20other%20ran%20without.%20After%20running%20for%20approximately%20three%20to%20five%20li%20%5Babout%201500%20to%202500%20metres%5D%2C%20the%20one%20without%20the%20ginseng%20de&f=false">documented</a> a trial of ginseng:</p>
<blockquote>
<p>[…] to evaluate the effect of genuine Shangdang ginseng, two persons were asked to run together. One was given the ginseng while the other ran without. After running for approximately three to five li [about 1,500-2,500 metres], the one without the ginseng developed severe shortness of breath, while the one who took the ginseng breathed evenly and smoothly.</p>
</blockquote>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/339359/original/file-20200603-133919-86vc4x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/339359/original/file-20200603-133919-86vc4x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/339359/original/file-20200603-133919-86vc4x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=900&fit=crop&dpr=1 600w, https://images.theconversation.com/files/339359/original/file-20200603-133919-86vc4x.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=900&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/339359/original/file-20200603-133919-86vc4x.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=900&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/339359/original/file-20200603-133919-86vc4x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1131&fit=crop&dpr=1 754w, https://images.theconversation.com/files/339359/original/file-20200603-133919-86vc4x.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1131&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/339359/original/file-20200603-133919-86vc4x.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1131&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Ginseng has long been used to treat people, as documented in this 17th century text.</span>
<span class="attribution"><a class="source" href="https://wellcomecollection.org/works/swtfrfwu">Wellcome Collection</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>This observational study is also the first recorded example of a <a href="https://methods.sagepub.com/reference/encyclopedia-of-survey-research-methods/n102.xml">control group</a>. </p>
<p>A control group can be patients who are not treated at all, patients who receive a standard treatment compared to a new one, or patients who receive a placebo (a treatment or substance designed to have no therapeutic effect). </p>
<p>Having a control group is one of the cornerstones of modern clinical trials.</p>
<p>An example of a control group in COVID-19 research is this recent <a href="http://www.ajtmh.org/docserver/fulltext/10.4269/ajtmh.20-0375/tpmd200375.pdf?expires=1591156982&id=id&accname=guest&checksum=32ABE0175BD9A7C2DFBF27F0CD5A4959">study</a>. People with diabetes hospitalised for COVID-19 were divided into those receiving the drug metformin and those not receiving it (the control group).</p>
<p>Back to ginseng. Today, it is a popular herbal remedy. As to whether it improves stamina, a recent review found some evidence ginseng might help men with <a href="https://pubmed.ncbi.nlm.nih.gov/29633089/?from_term=ginseng+erectile+dysfunction&from_sort=date&from_pos=6">erectile dysfunction</a>.</p>
<h2>Rhubarb in 18th-century England</h2>
<figure class="align-left zoomable">
<a href="https://images.theconversation.com/files/339363/original/file-20200603-133902-t0klhx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/339363/original/file-20200603-133902-t0klhx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/339363/original/file-20200603-133902-t0klhx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=1033&fit=crop&dpr=1 600w, https://images.theconversation.com/files/339363/original/file-20200603-133902-t0klhx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=1033&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/339363/original/file-20200603-133902-t0klhx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=1033&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/339363/original/file-20200603-133902-t0klhx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1299&fit=crop&dpr=1 754w, https://images.theconversation.com/files/339363/original/file-20200603-133902-t0klhx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1299&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/339363/original/file-20200603-133902-t0klhx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1299&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Rhubarb, seen in this 16th century text, has been used as a laxative for thousands of years.</span>
<span class="attribution"><a class="source" href="https://wellcomecollection.org/works/wzkk96pv">Wellcome Collection</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>Rhubarb roots have been used as a laxative for <a href="https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/rhubarb">more than 5,000 years</a>, including in 18th-century England.</p>
<p><a href="https://www.jameslindlibrary.org/articles/caleb-hillier-parry-1755-1822/">Caleb Parry</a>, an English physician working in Bath, wanted to know whether locally grown rhubarb was as good as the more expensive Turkish variety. </p>
<p>In 1786, he ran a <a href="https://www.jameslindlibrary.org/parry-ch-1786/">study</a> in which he switched the type of rhubarb he gave to each patient at different times. He then compared each patient’s symptoms while eating each type of rhubarb. He concluded there was no advantage in using the Turkish version.</p>
<p>This is the first published example of a <a href="https://www.bmj.com/content/316/7146/1719">crossover trial</a> (a study where the participants receive each treatment at different times).</p>
<p>Today, we know rhubarb roots and stems are rich in <a href="https://onlinelibrary.wiley.com/doi/abs/10.1002/med.21391">anthraquinones</a>, which have a <a href="https://pubmed.ncbi.nlm.nih.gov/30000922/?from_term=rhubarb+laxative&from_sort=date&from_pos=7">laxative effect</a>.</p>
<h2>Early 20th-century randomised trial</h2>
<p><a href="https://www.medicalnewstoday.com/articles/325261">Beriberi</a>, a disease that can have lasting effects on the nervous system and heart, was common in Southeast Asia in the early part of the 20th century. </p>
<p>In 1905 a beriberi outbreak <a href="https://www.jameslindlibrary.org/articles/the-contribution-of-william-fletchers-1907-report-to-finding-a-cause-and-cure-for-beriberi/">occured</a> at the Kuala Lumpur Lunatic Asylum. At that time William Fletcher was the district surgeon. He realised the outbreak provided an excellent opportunity to run an experiment (which we now know is just a bit unethical).</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/looking-back-on-the-chequered-past-of-drug-trials-14883">Looking back on the chequered past of drug trials</a>
</strong>
</em>
</p>
<hr>
<p>Each patient was assigned a number. Those with even numbers were sent to one ward and given brown unpolished rice to eat. Those with odd numbers went to another ward and given white polished rice.</p>
<p>At the end of the experiment, 15% of the patients who ate the white rice died of beriberi; none given brown rice died.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/health-check-can-vitamins-supplement-a-poor-diet-62291">Health Check: can vitamins supplement a poor diet?</a>
</strong>
</em>
</p>
<hr>
<p>This is a very early example of <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3136079/">randomisation</a> in a clinical trial, where one group is chosen at random to receive a treatment.</p>
<p>Randomisation is another very important factor in good clinical trial design.</p>
<p>Today we know beriberi is caused by a deficiency in thiamine (vitamin B1) and a white rice diet is deficient in <a href="https://www.medlink.com/article/thiamine_deficiency">thiamine</a>.</p>
<h2>Tuberculosis and the randomised controlled trial</h2>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/339368/original/file-20200603-133924-mvmvrm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/339368/original/file-20200603-133924-mvmvrm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/339368/original/file-20200603-133924-mvmvrm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=917&fit=crop&dpr=1 600w, https://images.theconversation.com/files/339368/original/file-20200603-133924-mvmvrm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=917&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/339368/original/file-20200603-133924-mvmvrm.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=917&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/339368/original/file-20200603-133924-mvmvrm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1152&fit=crop&dpr=1 754w, https://images.theconversation.com/files/339368/original/file-20200603-133924-mvmvrm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1152&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/339368/original/file-20200603-133924-mvmvrm.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1152&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Sir Austin Bradford Hill, whose tuberculosis trial has features of trials we see today.</span>
<span class="attribution"><a class="source" href="https://wellcomecollection.org/works/j983a8yj">Wellcome Collection</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p><a href="https://academic.oup.com/jnci/article/91/1/11/2549240">Sir Austin Bradford Hill</a>, an English epidemiologist and statistician, conducted the first randomised controlled trial in 1948. The <a href="https://www.jameslindlibrary.org/medical-research-council-1948b/">trial</a> was to treat the lung disease tuberculosis.</p>
<p>Bradford Hill decided whether a patient should be treated with the antibiotic streptomycin plus bed rest, or bed rest alone, by using a table of random numbers.</p>
<p>The investigators didn’t know which patient got each treatment; details were in sealed envelopes. Patients were not told they were in a trial.</p>
<p>Using sealed envelopes is an example of what we now call <a href="https://www.bmj.com/content/355/bmj.i5663">allocation concealment</a>. Making sure neither investigators nor patients know which treatment they are receiving is called <a href="https://ebn.bmj.com/content/16/3/70">blinding</a>. These are now standard features of randomised controlled trials.</p>
<p>Randomised controlled trials are the “gold standard” of clinical trial designs, due to the use of both a control group and randomisation.</p>
<p>Decades later, researchers have <a href="https://pubmed.ncbi.nlm.nih.gov/32470486">used</a> a randomised controlled trial to test the drug ruxolitinib in patients with severe COVID-19.</p>
<p>So, although Bradford Hill conducted the first randomised controlled trial, it was based on hundreds of years of people working out why things like a control group and randomisation are so important.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/randomised-control-trials-what-makes-them-the-gold-standard-in-medical-research-78913">Randomised control trials: what makes them the gold standard in medical research?</a>
</strong>
</em>
</p>
<hr>
<img src="https://counter.theconversation.com/content/139666/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Adrian Esterman does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Early clinical trials into ginseng, rhubarb and rice paved the way for testing coronavirus treatments today.Adrian Esterman, Professor of Biostatistics, University of South AustraliaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1358762020-05-11T11:49:35Z2020-05-11T11:49:35ZWhy the military can use emergency powers to treat service members with trial COVID-19 drugs<figure><img src="https://images.theconversation.com/files/331536/original/file-20200429-51489-1s4lh0.jpg?ixlib=rb-1.1.0&rect=8%2C0%2C5431%2C3637&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Military medical personnel have helped support hospitals with heavy patient loads.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/military-medical-personnel-including-u-s-army-reserve-and-news-photo/1221203883?adppopup=true">John Moore/Getty Images</a></span></figcaption></figure><p><a href="https://www.ncbi.nlm.nih.gov/books/NBK225082/#ddd00035">Infectious</a> <a href="https://academic.oup.com/cid/article/44/3/424/314476">disease</a> has always been one of the military’s <a href="https://www.ncbi.nlm.nih.gov/books/NBK225082/">greatest threats</a>. By <a href="https://www.army.mil/article/210420/worldwide_flu_outbreak_killed_45000_american_soldiers_during_world_war_i">its own</a> estimates, the U.S. Army lost almost as many soldiers from the 1918 flu as died on the battlefields of the first World War.</p>
<p>Troops are at risk during an outbreak due to the <a href="https://academic.oup.com/jid/article-abstract/82/1/72/824150?redirectedFrom=fulltext">tight quarters</a> in which they <a href="https://phc.amedd.army.mil/PHC%20Resource%20Library/Barracks%20Layout%20Jan%202010.pdf">live</a> and <a href="https://maritime.org/doc/submed/chap20.htm">work</a>. It is therefore not surprising that all branches of the service – <a href="https://www.militarytimes.com/news/coronavirus/2020/04/23/public-health-emergency-declared-for-us-troops-stationed-across-djibouti-base-cluster/">Army</a>, <a href="https://www.military.com/daily-news/2020/04/23/more-25-navy-ships-now-have-sailors-infected-coronavirus.html">Navy</a>, <a href="https://www.marinecorpstimes.com/news/coronavirus/2020/04/22/the-corps-has-halved-the-number-of-recruits-shipping-to-boot-camp-and-wants-them-to-self-isolate-for-14-days/">Marines</a>, <a href="https://www.airforcetimes.com/news/your-air-force/2020/04/01/air-force-academy-eases-restrictions-after-2-suicides/">Air Force</a> and <a href="https://www.middletownpress.com/news/article/32-U-S-Coast-Guard-members-have-coronavirus-as-15177316.php">Coast Guard</a> – have been <a href="https://time.com/5816219/white-house-hydroxychloroquine-covid">hit hard</a> by COVID-19. The military has also played an important role in responding to the virus, from evacuating State Department officials from Wuhan in <a href="https://www.defense.gov/Explore/Spotlight/Coronavirus/DOD-Response-Timeline/">January</a> to its current role <a href="https://www.defense.gov/Explore/News/Article/Article/2154305/corps-of-engineers-takes-on-28-covid-19-bed-facilities/">building and staffing civilian field hospitals</a> and <a href="https://www.defense.gov/Explore/News/Article/Article/2146685/army-deploys-medical-task-forces-to-help-hard-hit-communities/">augmenting</a> civilian research teams.</p>
<p>To <a href="https://time.com/5821729/coronavirus-hits-us-military/">mitigate any risk</a>, the Department of Defense has enforced rigorous <a href="https://www.armytimes.com/news/coronavirus/2020/04/24/west-point-plans-to-mass-test-and-soft-quarantine-cadets-coming-back-to-graduate/">social distancing policies</a> and a <a href="https://www.militarytimes.com/news/your-military/2020/04/18/dod-travel-ban-extended-to-june-30/">military-wide travel ban</a> halting nonessential deployments.</p>
<h2>New treatments</h2>
<p>But in addition to measures aimed at keeping people away from sources of infection, the military is also treating active duty personnel who become infected. Because the COVID-19 virus is new, there are as yet no FDA approved treatments. As a result, military physicians are turning to either treatments approved for other <a href="https://www.washingtonexaminer.com/policy/defense-national-security/military-gives-covid-patients-chloroquine-and-surges-assets-to-new-york-city">conditions</a> or seeking <a href="https://clinicaltrials.gov/ct2/show/study/NCT04302766">access</a> to <a href="https://urldefense.proofpoint.com/v2/url?u=https-3A__www.militarytimes.com_news_your-2Dmilitary_2020_03_10_army-2Dsigns-2Dagreement-2Dwith-2Ddrug-2Dgiant-2Dgilead-2Don-2Dexperimental-2Dcovid-2D19-2Dtreatment_&d=DwMFaQ&c=sJ6xIWYx-zLMB3EPkvcnVg&r=yV7ArXT4ooMMfCcV3fg-GA&m=Q2qM-rfW9kd79x3mKFw_7oXsZ0231HlqPy2n6GJHNQE&s=3LaRfCeF9eoIT4u47VM2mng-qqqjpWNNd6v6ukn8NVo&e=">newly developed treatments,</a> such as the <a href="https://www.wearethemighty.com/news/army-success-covid-ebola-drug">antiviral Remdesivir</a>, which to date has received FDA <a href="https://www.fda.gov/media/137564/download">emergency use approval</a> only for COVID-19 patients with severe conditions. That presents a significant legal challenge due to existing laws protecting military personnel by recognizing that their obligation to follow orders reduces their ability to provide informed consent.</p>
<p>As an expert in <a href="https://www.law.ufl.edu/faculty/jennifer-bard">public health law</a> and human subject research, I study the tension between protecting participants of biomedical research and responding quickly to emerging threats. But I have also had personal experience with the events that led to the passing of the law that allows the military to work with the FDA in order to get emergency authorization to respond quickly to emerging threats.</p>
<h2>Gulf War Syndrome</h2>
<p>In 1998, I was working for now U.S. Senator, then Connecticut Attorney General, Richard Blumenthal when I met <a href="https://www.courant.com/news/connecticut/hc-xpm-1999-01-15-9901150362-story.html">Russ Dingle</a> and <a href="https://www.nwitimes.com/news/local/anthrax-vaccine-a-deadly-defense/article_696fe42f-17f7-5626-9703-ecaee934431f.htm">Thomas “Buzz” Rempfer</a>, two remarkable airmen who filed a whistleblower complaint seeking protection from what they described as forced participation in an unlawful research experiment. Specifically, they asserted that the Department of Defense was mandating that all active duty personnel be vaccinated against anthrax using a product, <a href="https://www.warrelatedillness.va.gov/education/factsheets/anthrax.pdf">AVA</a>, <a href="https://dash.harvard.edu/handle/1/8965604">not yet approved by the FDA</a> for the purpose the Army was now using it.</p>
<p>The vaccine had been in use <a href="https://dash.harvard.edu/bitstream/handle/1/8965604/Corrigan.pdf?sequence=1&amp;isAllowed=y">since the 1970s</a> to <a href="https://www.rand.org/pubs/research_briefs/RB7534.html">protect wool workers and veterinarians</a> at risk from touching naturally occurring anthrax spores, but had not been approved for protection against inhaling them, a method of spread <a href="http://content.time.com/time/magazine/article/0,9171,1001161,00.html">reportedly developed by</a> Iraqi scientists as a <a href="https://www.pnas.org/content/100/8/4355">bioweapon</a>. But many in the military were reluctant to be vaccinated because of their concern that it might be a cause of <a href="https://www.salon.com/2003/12/10/anthrax_20/">Gulf War Syndrome</a>. To <a href="https://www.publichealth.va.gov/exposures/gulfwar/sources/vaccinations.asp">this day</a>, there is no agreement about the <a href="https://www.publichealth.va.gov/exposures/gulfwar/sources/vaccinations.asp">specific symptoms</a>, let alone cause, of Gulf War Syndrome.</p>
<p>A 2000 <a href="https://www.nap.edu/catalog/9953/gulf-war-and-health-volume-1-depleted-uranium-sarin-pyridostigmine">report by the well-respected Institute of Medicine</a> found <a href="https://www.theguardian.com/environment/2001/jul/30/internationalnews">“no conclusive link to the vaccine</a>.” But the causal connection seemed plausible to many sufferers, especially given the <a href="https://www.propublica.org/article/the-children-of-agent-orange">continuing emergence</a> of long-term harm suffered by veterans of the Vietnam War and their children from exposure to Agent Orange. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/331799/original/file-20200430-42903-vosv76.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/331799/original/file-20200430-42903-vosv76.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/331799/original/file-20200430-42903-vosv76.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/331799/original/file-20200430-42903-vosv76.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/331799/original/file-20200430-42903-vosv76.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/331799/original/file-20200430-42903-vosv76.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/331799/original/file-20200430-42903-vosv76.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">U.S. soldiers in the first Gulf War complained of a series of acute and chronic conditions after the conflict.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/soldiers-arrive-at-a-burning-oil-refinery-in-al-khafji-news-photo/541790116?adppopup=true">Patrick Durand/Sygma via Getty Images</a></span>
</figcaption>
</figure>
<p>The whistleblower’s primary claim was that the anthrax vaccination program was “research” and therefore the army was required to abide by two different protections. The first, called the <a href="https://mrdc.amedd.army.mil/assets/docs/orp/irbo/IRB_Policies_Procedures_2018_Common_Rule.pdf">Common Rule</a>, is a law establishing that all research conducted by the federal government require the informed consent <a href="https://onlinelibrary.wiley.com/doi/epdf/10.1197/j.aem.2005.05.037">of participants</a>. Their second claim was that even if it was being used as a preventative measure, the Department of Defense was constrained by a 1998 law passed in direct response to concerns over possible links between unapproved drugs and Gulf War Syndrome. It prohibited “the <a href="https://biotech.law.lsu.edu/cases/vaccines/Doe_v_Rumsfeld_I.htm">administration of investigational new drugs</a>, or drugs unapproved for their intended use, to service members without their informed consent” unless consent was waived by the president.</p>
<p>Blumenthal <a href="https://www.courant.com/news/connecticut/hc-xpm-2001-03-23-0103231252-story.html">wrote</a> to the secretary of defense warning him that administering an unapproved vaccine risked violating both laws and demanding that the research be stopped. That letter became part of <a href="https://www.rand.org/pubs/monograph_reports/MR1018z9/MR1018.9.chap2.html">a larger debate over whether the military’s need for force protection exceeded the risks to any individual serviceperson</a>.</p>
<h2>Emergency use</h2>
<p>In 2003, Colonel Rempfer and six other <a href="https://www.nti.org/gsn/article/plaintiffs-in-anthrax-vaccine-lawsuit-are-named/">at first unnamed</a> plaintiffs <a href="https://scholarship.law.ufl.edu/facultypub/295/">brought suit</a> in federal court which resulted in a preliminary <a href="https://biotech.law.lsu.edu/cases/vaccines/Doe_v_Rumsfeld_I.htm">injunction</a> halting the vaccine program. Responding to the lawsuit, the Department of Defense denied that they were conducting research and <a href="https://www.rand.org/pubs/research_briefs/RB7534.html">claimed the authority</a> to waive consent because it was necessary to prevent infection with weaponized anthrax.</p>
<p>But in winning the battle, those seeking to stop the vaccine program lost the war. The Department of Defense appealed to Congress for a workaround. It resulted in the passing of the <a href="https://www.govinfo.gov/app/details/PLAW-108publ276">BioShield Act in 2004</a>, creating the <a href="https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/mcm-emergency-use-authorities">Emergency Use Authorization</a>. This gave the FDA authority to recharacterize the status of a drug or vaccine from investigational to approved for emergency use. In December of 2005 it issued a “<a href="https://www.cidrap.umn.edu/news-perspective/2005/12/fda-reaffirms-worth-dod-anthrax-vaccine">final order concluding that [the Anthrax Vaccine] was the best available medical countermeasure to the potential military emergency</a>.” Although Col. Rempfer filed <a href="https://biotech.law.lsu.edu/cases/vaccines/rempfer.pdf">a lawsuit</a> to protest the FDA’s decision, it was to no avail and shortly afterwards the Department of Defense resumed the vaccine program. <a href="https://www.journalinquirer.com/connecticut_and_region/efforts-continue-to-posthumously-promote-ehartford-man-who-opposed-military/article_f6607ffd-3b84-55cb-9570-e1dc3b6e9339.html">Col. Dingle</a> died of cancer in 2008, but Col. Rempfer <a href="https://www.hsaj.org/articles/102">remained critical of the </a><a href="https://www.hsaj.org/articles/102">anthrax vaccine</a> program and still actively advocates on behalf of past and future military personnel.</p>
<h2>A compromise</h2>
<p>Since the passage of the BioShield Act, Congress <a href="https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/mcm-emergency-use-authorities">has continued to support the FDA’s </a> authority to make unapproved drugs available in response to new threats. <a href="https://www.washingtonpost.com/news/to-your-health/wp/2017/11/09/controversy-erupts-over-plan-to-let-pentagon-use-unapproved-drugs-on-battlefield/">In 2017</a>, the Department of Defense sought power to unilaterally authorize use of unapproved drugs in battlefield situations. In the face of FDA objections to this level of autonomy, Congress created <a href="https://www.fdli.org/2018/08/update-public-law-115-92-a-new-era-of-collaboration-between-dod-and-fda/">a compromise measure</a> memorialized in a <a href="https://www.fda.gov/about-fda/domestic-mous/mou-225-19-001">Memorandum of Understanding</a> that allows the Department of Defense broad authority to declare the need for emergency use permission and <a href="https://www.engage.hoganlovells.com/knowledgeservices/news/fda-and-dod-strengthen-collaboration-for-medical-products-with-military-applications-that-could-also-be-expanded-to-the-general-population">request that the FDA</a> “take actions to expedite the development of a medical product.” But final authority to issue an emergency use order rests with the president.</p>
<p>It is because of the servicemen committed to the preservation of informed consent that troops today have early access to potential COVID-19 drugs and vaccines while still respecting their vulnerability as patients without the complete ability to give informed consent.</p><img src="https://counter.theconversation.com/content/135876/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jennifer Bard does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Army physicians are turning to drugs approved for other conditions or newly developed treatments such as the antiviral Remdesivir to treat infected personnel.Jennifer Bard, Visiting Professor of Law, University of FloridaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1347262020-03-30T16:25:00Z2020-03-30T16:25:00ZCoronavirus vaccine: here are the steps it will need to go through during development<figure><img src="https://images.theconversation.com/files/324019/original/file-20200330-146683-1cvrccs.jpg?ixlib=rb-1.1.0&rect=35%2C28%2C4756%2C3161&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A vaccine must go through six crucial steps.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/doctor-nurse-scientist-hand-blue-nitrile-1489783262">PhotobyTawat/ Shutterstock</a></span></figcaption></figure><p>Since humans haven’t previously been exposed to the novel coronavirus (<a href="https://www.who.int/health-topics/coronavirus">SARS-CoV-2</a>), our bodies aren’t well equipped to deal with being infected by it. A vaccine would allow the body to safely develop an immune response to COVID-19 that could prevent or control infection.</p>
<p>But it takes time to develop safe and effective vaccines – usually five to ten years on average. Despite promising reports about <a href="https://www.theguardian.com/world/2020/mar/25/coronavirus-vaccine-when-will-it-be-ready-trials-cure-immunisation">potential coronavirus vaccines</a> being developed worldwide, it could still take an estimated <a href="https://www.businessinsider.fr/us/us-top-virus-expert-coronavirus-vaccine-12-18-months-away-2020-3">12-18 months</a> to develop one. </p>
<p>It’s becoming quicker to develop new vaccines than it was in the past as we can build on research from vaccines used for other diseases. During outbreaks, more resources and funding may also become available, which can speed up the process. Products might also be considered for use even before being formally granted licences to control the disease in severely affected areas during emergencies.</p>
<p>The development of a potential novel coronavirus vaccine is being partly led by experts who were already developing vaccines for other coronaviruses. This type of virus was identified as a possible <a href="https://www.who.int/activities/prioritizing-diseases-for-research-and-development-in-emergency-contexts">cause of the next big pandemic</a> as the other coronaviruses <a href="https://www.who.int/ith/diseases/sars/en/">SARS</a> and <a href="https://www.who.int/news-room/fact-sheets/detail/middle-east-respiratory-syndrome-coronavirus-(mers-cov)">MERS</a> have been responsible for two global outbreaks in the last 20 years. Research on vaccines for these coronaviruses was already <a href="https://www.nature.com/articles/d41587-020-00005-z">undergoing clinical trials</a>. </p>
<p>The first new vaccine to <a href="https://time.com/5790545/first-covid-19-vaccine/">enter human trials for COVID-19</a> was developed by the US firm Moderna Therapeutics. About <a href="https://www.who.int/blueprint/priority-diseases/key-action/novel-coronavirus/en/">35 other companies and academic institutions</a> are also working on COVID-19 vaccines. Most are currently in “pre-clinical testing”, including one being developed by a <a href="https://www.theguardian.com/society/2020/mar/19/uk-drive-develop-coronavirus-vaccine-science">team of researchers</a> at the University of Oxford. The vaccine candidate was identified in January and is nearing the clinical testing phase. </p>
<p>During development, a vaccine needs to go through the following steps:</p>
<h2>1. Basic understanding of the virus</h2>
<p>In the past, most studies of human viruses looked at how the virus altered or affected human or animal cells in the lab. Scientists first identify the proteins and sugars on the surface of the viruses or infected cells, then study whether these proteins can be used to produce an immune response.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/324022/original/file-20200330-146705-ttnxps.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/324022/original/file-20200330-146705-ttnxps.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/324022/original/file-20200330-146705-ttnxps.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/324022/original/file-20200330-146705-ttnxps.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/324022/original/file-20200330-146705-ttnxps.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/324022/original/file-20200330-146705-ttnxps.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/324022/original/file-20200330-146705-ttnxps.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Knowing the virus’s genetic sequence has also helped develop coronavirus test kits.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/analysis-dna-sequences-genetic-laboratory-112365716">science photo/ Shutterstock</a></span>
</figcaption>
</figure>
<p>In the present case, this stage was made easier for researchers after Chinese scientists found and published the <a href="https://www.who.int/csr/don/12-january-2020-novel-coronavirus-china/en/">genetic sequence of novel coronavirus</a> in January. Researchers worldwide have been able to identify the structure of proteins that make up the virus, create a genetic history of the family of viruses, and determine when the first human was infected. It also enabled diagnostic testing kits to be developed, and lets researchers identify potential treatment options.</p>
<h2>2. Vaccine candidates</h2>
<p>This may involve isolating the live virus before inactivating or weakening it and then determining whether this modified virus, which is known as a vaccine candidate, might produce immunity in people. </p>
<p>Sometimes the live virus is not part of the process. Instead, its genetic sequence is used to make the vaccine. The genetic sequence can also be used to make <a href="https://www.sciencedirect.com/topics/neuroscience/recombinant-proteins">recombinant proteins</a>, a vaccine production method that has been used before for vaccines like <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3854212/">hepatitis B</a>. </p>
<p>Researchers now know how to manufacture and test the relevant vaccine and check it has been made properly. They even know about likely doses, including how many doses will be needed to build immunity. This background knowledge speeds up the development of each new vaccine made using the same technology.</p>
<h2>3. Pre-clinical testing</h2>
<p>Initial safety testing is usually carried out in <a href="https://academic.oup.com/ilarjournal/article/56/1/53/661264">animals</a> to give an idea of responses in humans. These are also used to see how effective the vaccine is at preventing the disease, and allows researchers to adapt the vaccine. </p>
<p>During an outbreak, different research groups often work together to speed up this process. </p>
<h2>4. Clinical trials – testing in humans</h2>
<p>This step is where many promising potential vaccines fail. There are three phases of a clinical trial:</p>
<ol>
<li>Testing on a few dozen healthy volunteers, looking at how safe the vaccine is, and if it has any adverse effects;</li>
<li>Testing on several hundred people for efficacy (a “target population” who are ideally those most at risk of the disease);</li>
<li>Testing on several thousand people for efficacy and safety.</li>
</ol>
<p>Through these phases the vaccine needs to show it’s safe, leads to a strong immune response, and provides effective protection against the virus. During an outbreak, experimental vaccines may be used in severely affected populations if they’re at high risk of disease, before progressing to regulatory approval.</p>
<h2>5. Regulatory approvals</h2>
<p>If regulators have approved similar products before, approval can be accelerated – although this is not likely for COVID-19. Use of a vaccine before full licensure can be considered in a public health emergency. </p>
<h2>6.Production</h2>
<p>Once a vaccine has been produced at a small scale and passed safety tests, it can be used in clinical trials. However, significant manufacturing capacity, such as infrastructure, personnel and equipment, will be needed to produce large quantities of a vaccine for use. Quality control is also needed. All of these processes are very carefully monitored. Once licensed, policy must be developed to decide how to prioritise those who should be vaccinated, such as those in the most high-risk groups and locations.</p>
<p>Along the way, if any of these vaccine “candidates” are shown to be unsafe or ineffective, researchers must return to the laboratory to develop a new candidate. This is why vaccine development can be a long and uncertain process.</p><img src="https://counter.theconversation.com/content/134726/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Samantha Vanderslott receives funding from the National Institute for Health Research (NIHR) and the New Venture Fund. She is also a steering committee member for the Vaccination Acceptance Research Network (VARN).</span></em></p><p class="fine-print"><em><span>Andrew Pollard chairs the Department of Health and Social Care's Joint Committee on Vaccination and Immunisation and is a member of the World Health Organisation's SAGE.</span></em></p><p class="fine-print"><em><span>Tonia Thomas does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Researchers around the world are working hard on developing a vaccine – but the process may still take 12-18 months. Here’s why.Samantha Vanderslott, Postdoctoral Researcher in Social Sciences, University of OxfordAndrew Pollard, Professor of Paediatric Infection and Immunity, University of OxfordTonia Thomas, Vaccine Knowledge Project Manager, University of OxfordLicensed as Creative Commons – attribution, no derivatives.