tag:theconversation.com,2011:/africa/topics/vaccine-development-1086/articlesVaccine development – The Conversation2023-09-21T21:27:36Ztag:theconversation.com,2011:article/2085382023-09-21T21:27:36Z2023-09-21T21:27:36ZLyme disease: The pathogen’s cunning strategies for persistent infection offer clues for vaccine development<figure><img src="https://images.theconversation.com/files/547386/original/file-20230911-25-n5os9t.JPG?ixlib=rb-1.1.0&rect=65%2C23%2C1709%2C1158&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The black-legged tick is the vector that spreads Lyme disease. Its bite can infect humans with the Borrelia burgdorferi bacterium.</span> <span class="attribution"><span class="source">(Jim Gathany/CDC)</span></span></figcaption></figure><iframe style="width: 100%; height: 100px; border: none; position: relative; z-index: 1;" allowtransparency="" allow="clipboard-read; clipboard-write" src="https://narrations.ad-auris.com/widget/the-conversation-canada/lyme-disease-the-pathogens-cunning-strategies-for-persistent-infection-offer-clues-for-vaccine-development" width="100%" height="400"></iframe>
<p>Lyme disease is the leading <a href="https://www.who.int/news-room/fact-sheets/detail/vector-borne-diseases">vector-borne disease</a> — meaning diseases that are transmitted to humans from another organism like a tick or mosquito — in <a href="https://doi.org/10.1186/s12889-019-7069-6">North America and Europe</a>. </p>
<p><a href="https://doi.org/10.3201/eid2702.202731">New human cases are estimated</a> at over <a href="http://dx.doi.org/10.15585/mmwr.ss6622a1">400,000 in the United States each year</a>. Canada has experienced a drastic increase in human cases, <a href="https://www.canada.ca/en/public-health/services/diseases/lyme-disease/surveillance-lyme-disease.html#a5">from 266 cases in 2011 to 3,147 in 2021</a>, as the habitat of its vector, a tick, expands north. </p>
<p>The initial symptoms of human Lyme disease can be vague, such as fever, headache, fatigue and often rash. It is a potentially serious condition that can affect multiple systems in the body — including the heart, nervous system and joints — and can become a chronic illness.</p>
<p>Lyme disease is caused by a unique, spiral-shaped (spirochete) bacterium called <a href="https://doi.org/10.1099/00207713-34-4-496"><em>Borrelia burgdorferi</em></a>. <em>B. burgdorferi</em> cannot survive in the environment on its own. For <a href="https://doi.org/10.21775/cimb.042.473">survival and transmission</a>, it requires susceptible hosts (usually small mammals or birds) and a <a href="https://doi.org/10.1056/NEJM198303313081301">specific vector</a>: the black-legged tick, also called the deer tick.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/535388/original/file-20230703-257464-m0lz6y.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/535388/original/file-20230703-257464-m0lz6y.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=420&fit=crop&dpr=1 600w, https://images.theconversation.com/files/535388/original/file-20230703-257464-m0lz6y.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=420&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/535388/original/file-20230703-257464-m0lz6y.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=420&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/535388/original/file-20230703-257464-m0lz6y.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=528&fit=crop&dpr=1 754w, https://images.theconversation.com/files/535388/original/file-20230703-257464-m0lz6y.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=528&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/535388/original/file-20230703-257464-m0lz6y.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=528&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Lyme disease infectious cycle: Adult ticks lay egg sacs that can hatch thousands of tick larvae. Larvae are not born with Borrelia burgdorferi but can acquire the bacterium when they feed on an infected host. After feeding, larvae molt to nymphs which must feed once to molt to adults. Female adult ticks also feed once before laying the egg sac. Nymphs and adult ticks can transmit B. burgdorferi to susceptible hosts while feeding.</span>
<span class="attribution"><span class="source">(BioRender)</span></span>
</figcaption>
</figure>
<h2>Evading the immune system</h2>
<p><em>B. burgdorferi</em> must survive extremely diverse conditions over the course of its transmission and infection cycle: from host to tick vector, and then into new hosts. </p>
<p>This bacterium senses and responds to its surroundings, most notably by <a href="https://doi.org/10.1128/iai.70.7.3382-3388.2002">modifying its appearance</a> by changing the <a href="https://doi.org/10.1073/pnas.92.7.2909" title="). _B. burgdorferi_ has over [50 surface-exposed proteins](https://doi.org/10.1128/jb.00658-16 "">proteins on its outer surface</a> to <a href="https://doi.org/10.1111/j.1574-695X.2012.00980.x">help it survive</a> in either <a href="https://doi.org/10.1038/s41467-023-35897-3">the tick</a> or the host.</p>
<p>When a tick infected by <em>B. burgdorferi</em> bites and feeds on a vertebrate host, it provides a signal for the bacteria to switch its proteins to those required to infect the host, and to begin migrating through the tick and into the bite site. This process takes between <a href="https://doi.org/10.4269/ajtmh.1995.53.397">36 and 72 hours</a>. </p>
<p>However, many of these proteins are recognized by the host as foreign, and the host’s immune system works to try to clear the infection. This includes a strong, antibody response targeted against <em>B. burgdorferi</em>. </p>
<p>Despite these immune responses, <em>B. burgdorferi</em> is able to cause long-term infections. In natural host reservoirs — the animals that the bacterium usually finds itself in via tick bites, such as small rodents — these infections do not cause diseases like those seen in humans and other <a href="https://doi.org/10.1016/j.idc.2007.12.013">non-natural reservoirs</a>. </p>
<p>In fact, the bacteria itself does not produce any products that would be <a href="https://doi.org/10.1016/j.cll.2015.07.004">toxic to its hosts</a>, either natural or non-natural. Yet chronic infection in humans can lead to <a href="https://doi.org/10.1038/nrdp.2016.90">Lyme neuroborreliosis, carditis and Lyme arthritis</a>.</p>
<figure class="align-center ">
<img alt="Bacteria that look like bright green and yellow squiggles against a dark green background" src="https://images.theconversation.com/files/548570/original/file-20230915-23-4ysjok.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/548570/original/file-20230915-23-4ysjok.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=612&fit=crop&dpr=1 600w, https://images.theconversation.com/files/548570/original/file-20230915-23-4ysjok.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=612&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/548570/original/file-20230915-23-4ysjok.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=612&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/548570/original/file-20230915-23-4ysjok.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=770&fit=crop&dpr=1 754w, https://images.theconversation.com/files/548570/original/file-20230915-23-4ysjok.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=770&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/548570/original/file-20230915-23-4ysjok.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=770&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Microscopic image of Lyme disease bacteria Borrelia burgdorferi. In this photo, immunofluorescent antibodies have been used to change the colour of spirochetes that express different outer surface proteins.</span>
<span class="attribution"><span class="source">(NIAID)</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
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<p>How then, are these bacteria able to cause such a devastating disease in humans and other animals, but not in their natural host reservoirs?</p>
<p>While there is still much to learn about <em>B. burgdorferi</em>, we know of several factors that play a role in the <a href="https://doi.org/10.1038/nrdp.2016.90">range of disease it causes</a>. These include:</p>
<ul>
<li>its genetic make-up, </li>
<li>its ability to access various tissues (such as the joints, heart and nervous system) due to its <a href="https://doi.org/10.1128/iai.01228-12">ability to move around (motility)</a>, and </li>
<li>the immune response of the host. </li>
</ul>
<p>Apart from motility, <em>B. burgdorferi</em> also protects itself from the strong <em>B. burgdorferi</em>-specific targeted antibody response of its host’s immune system by changing the appearance of the main outer surface protein expressed during persistent infection in a process called <a href="https://doi.org/10.1128/iai.66.8.3698-3704.1998">antigenic variation</a>.</p>
<h2>How Lyme disease is perpetuated</h2>
<p>In addition to antigenic variation, <em>B. burgdorferi</em> bacteria can also change their DNA by <a href="https://doi.org/10.1073/pnas.0402745101">exchanging genetic information, a process also known as gene transfer</a>. This process allows these bacteria to further alter their <a href="https://doi.org/10.1128/mbio.00153-10">appearance</a> <a href="https://doi.org/10.1534/genetics.111.130773">during infection</a> to avoid the host immune system.</p>
<p>This process works so well that these <em>B. burgdorferi</em> bacteria appear different enough to allow <a href="https://doi.org/10.7326/0003-4819-127-2-199707150-00006">re-infection</a> or even <a href="https://doi.org/10.1128/iai.01817-14">co-infection</a> (where multiple strains of B. burgdorferi infect a single host at the same time) of a vertebrate host, like a mouse or a human, despite the presence of specific antibodies to fight the bacterium.</p>
<p>In fact, in nature, the majority of host reservoirs and the ticks that carry the bacterium are infected with <a href="https://doi.org/10.1128/AEM.02296-15">multiple strains of <em>B. burgdorferi</em></a>. The ability of <em>B. burgdorferi</em> to reinfect and co-infect both ticks and hosts increases the spread of the bacteria in the environment as well as the chances that humans will encounter Lyme disease.</p>
<h2>Human cases of Lyme disease are increasing</h2>
<p>As a vector-borne pathogen, <em>B. burgdorferi</em> only infects individuals that are bitten by an infected tick. It is not transmitted from <a href="https://doi.org/10.1093/cid/ciz872">person to person</a>.</p>
<p>Environments that support black-legged/deer ticks are at risk of harbouring <em>B. burgdorferi</em>. In North America, these species of ticks are widely distributed throughout the eastern and midwestern United States. Recent <a href="https://doi.org/10.1093/jme/tjy104">geographic expansion</a> to the north is increasing the prevalence of Lyme disease <a href="https://doi.org/10.1503/cmaj.080148">in Canada</a>. </p>
<p>The increase of human Lyme disease cases highlights the failure of existing preventive strategies — such as minimizing exposure to tick habitats, performing diligent tick checks, and wearing suitable clothing when performing activities in known tick habitats — and emphasizes the need for an effective <a href="https://doi.org/10.21775/cimb.042.191">human vaccine</a>.</p>
<h2>A One Health approach</h2>
<p>At <a href="https://www.vido.org/">Vaccine and Infectious Disease Organization</a> at the University of Saskatchewan, we are taking a <a href="https://ipac-canada.org/one-health">One Health</a> approach by recognizing that human health is closely related to the health of animals and the shared environment. We are investigating the role of <em>B. burgdorferi</em>, ticks, and susceptible animals on the spread and survival of the Lyme disease bacterium. </p>
<p>It is important to mimic the natural infectious cycle as much as possible when identifying potential vaccine and drug targets. This is because the way host animals are infected (for example, artificial needle infection or natural tick bite) can produce drastic differences in the resulting infection. </p>
<p>Additionally, despite the prevalence of this disease, there are still many aspects of the infectious cycle that remain unknown due to the uniqueness of <em>B. burgdorferi</em> and a lack of knowledge about the tick vector. </p>
<p>For example, we recently learned that a <em>B. burgdorferi</em> protein is responsible for regulating the components necessary for the bacterium to infect vertebrates, including humans. The absence of this protein, among other things, leads to the <a href="https://doi.org/10.1038/s41467-023-35897-3">death of <em>B. burgdorferi</em> in ticks</a>, making it an exciting target for research investigation. </p>
<p>By learning more about the molecular mechanisms that change or reduce the severity of the disease caused by this bacterium, we can identify new targets for the prevention of human Lyme disease.</p><img src="https://counter.theconversation.com/content/208538/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jenny Wachter 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>The bacterium that causes Lyme disease is a master of disguise, changing its appearance to evade the immune system as it moves from the ticks that carry it to humans or animals.Jenny Wachter, Research scientist/Adjunct professor, University of SaskatchewanLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1958072023-02-07T13:33:23Z2023-02-07T13:33:23ZHow do you make a universal flu vaccine? A microbiologist explains the challenges, and how mRNA could offer a promising solution<figure><img src="https://images.theconversation.com/files/508472/original/file-20230206-31-mtkppf.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2309%2C1299&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Broad protection from a universal flu vaccine could replace seasonal flu shots.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/influenza-vaccine-vials-pattern-background-royalty-free-image/1365216790">Flavio Coelho/Moment via Getty Images</a></span></figcaption></figure><p>To everything there is a season, and for the flu, it’s wintertime. Flu cases <a href="https://www.cdc.gov/flu/about/season/flu-season.htm">peak between December and February</a>, and the flu vaccine is your best defense. Getting the vaccine means you <a href="https://www.cdc.gov/flu/prevent/keyfacts.htm">will be less sick</a> even if you get a breakthrough infection. </p>
<p>However, your immune system is in a constant race against the flu virus. Like the virus that causes COVID-19, influenza rapidly changes and mutates into new variants, so manufacturers have to update the flu shot to <a href="https://www.doi.org/10.1126/science.aaq0105">try to keep pace</a>. After identifying a new flu variant, it takes manufacturers about six months to update the vaccine – and in the meantime the virus can mutate again. This phenomenon is called <a href="https://doi.org/10.1146/annurev-virology-010320-044746">antigenic drift</a>, and can reduce the effectiveness of the flu vaccine for that season. </p>
<p>An ongoing threat is that a major change in the flu virus, or <a href="https://www.cdc.gov/flu/about/viruses/change.htm">antigenic shift</a>, could cause the next flu pandemic. This happens when a flu virus from animals, such as birds or swine, gains the ability to transmit between humans. Most people will have no immunity against this new animal-origin virus, so it could quickly spread into a pandemic. If that happens, the annual flu shot will not be effective and can’t be updated fast enough to stop a global spread.</p>
<p><a href="https://scholar.google.com/citations?user=eNprtJEAAAAJ&hl=en">I am a researcher</a> developing new vaccines to prevent future pandemics. Nearly 20 years ago, my lab and several others developed a vision of building a <a href="https://doi.org/10.1101%2Fcshperspect.a028845">universal influenza vaccine</a> that could give us the leading edge in the race against influenza and prevent the next flu pandemic by effectively combating any eventual flu strain. One potential way to do this is with messenger RNA, or mRNA.</p>
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<figcaption><span class="caption">A primary challenge in developing vaccines against influenza is how rapidly the virus mutates.</span></figcaption>
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<h2>What is a universal influenza vaccine?</h2>
<p>A universal influenza vaccine is one that does not need to be updated each year because it is designed to protect against all or most influenza variants. Scientists are exploring several ways to develop universal influenza vaccines. Most fall into <a href="https://doi.org/10.1093/infdis/jiy103">one of two buckets</a>. </p>
<p>The first includes vaccines that focus on conserved, or unchanging, parts of the virus. This strategy directs the immune system against parts of the virus, or antigens, that are shared among all variants and can’t mutate without weakening or killing the virus.</p>
<p>The second includes mosaic vaccines. These are like a cocktail of protein pieces taken from different variants. The blend is made up of versions of the protein hemagglutinin – essential to the influenza virus’s ability to infect cells – that is found in all flu variants circulating in animals and people. The goal is to induce immunity against nearly all variants so there will be fewer gaps in the immune system’s defenses for the virus to slip through.</p>
<h2>Using mRNA for a universal flu vaccine</h2>
<p>The recent success of mRNA vaccines for COVID-19 shows promise for their use in achieving the vision of an effective universal influenza vaccine. </p>
<p>There are 20 known subtypes of influenza. Prior to the development of mRNA vaccines, it wasn’t feasible to make a single flu vaccine against all 20 subtypes due to the complexities and costs in manufacturing. Unlike traditional vaccines, constructing and producing mRNA vaccines is rapid and simple because manufacturers don’t have to produce and purify the protein directly. Instead, mRNA vaccines provide the genetic sequence of the protein and then use the body’s own cells to generate that protein <a href="https://doi.org/10.1073/pnas.2123477119">in its natural structure</a>. This makes it relatively easy to incorporate any antigen or many antigens.</p>
<p>Recently, a team of researchers <a href="https://doi.org/10.1126/science.abm0271">designed a mosaic mRNA vaccine</a> with sequences from multiple versions of the hemagglutinin protein, each representing one of the 20 influenza subtypes. This vaccine induced broad immunity against each variant in mice and ferrets.</p>
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<figcaption><span class="caption">mRNA vaccines circumvent some of the manufacturing challenges traditional vaccines face.</span></figcaption>
</figure>
<p>Several research groups are also exploring the conserved antigen approach with mRNA vaccines. Animal studies have shown that it’s possible to design mRNA vaccines that can both focus immune responses against highly conserved, vulnerable parts of the virus and <a href="https://doi.org/10.1126/sciadv.adc9937">induce</a> <a href="https://doi.org/10.1016/j.ymthe.2020.04.018">broad immunity</a> against a wide range of different influenza subtypes. These include <a href="https://doi.org/10.1073/pnas.2206333119">avian flu viruses</a> that share many genetic sequences with human influenza. </p>
<p>Another promising approach uses <a href="https://give.uwmedicine.org/stories/designing-a-pandemic-free-future/">computational modeling</a> to leverage both conserved and mosaic approaches. This strategy displays multiple hemagglutinins from different influenza subtypes <a href="https://doi.org/10.3389/fimmu.2019.00022">on a nanoparticle</a>. Nanoparticles are structures that give researchers more precise control over how the immune system sees the viral antigens, subsequently allowing them to induce stronger immune responses against multiple variants. Here, both conserved and variable regions of the virus are exposed to the immune system and can lead to <a href="https://doi.org/10.1038/s41586-021-03365-x">broad immunity</a>.</p>
<h2>Obstacles to a universal flu mRNA vaccine</h2>
<p>There are still several challenges before a universal influenza mRNA vaccine can be made available. </p>
<p>For one, it is not clear which conserved antigens provide the broadest protection, and some don’t naturally induce strong immune responses. So, mRNA vaccines may need improvements like additional components that help activate immune cells. One such addition could include <a href="https://doi.org/10.1073/pnas.2217533119">using mRNA to express nanoparticles</a> that stimulate stronger immune responses against the conserved antigens presented by the vaccine.</p>
<p>The mosaic approach is also limited by the <a href="https://doi.org/10.1056/NEJMoa2022483">maximum dose possible</a> for mRNA vaccines, because higher doses could cause increased adverse reactions to the vaccine. When that dose gets divided into 20 or more antigens, the dose of one or more of those antigens may drop below the threshold needed for protection.</p>
<p>Scientists are working on these challenges, including by developing <a href="https://doi.org/10.1126/science.abq6562">new mRNA technologies</a> that work with a much lower dose. If mRNA vaccines work for universal protection from influenza, the same strategies could also <a href="https://theconversation.com/how-mrna-and-dna-vaccines-could-soon-treat-cancers-hiv-autoimmune-disorders-and-genetic-diseases-170772">apply to other frequently mutating viruses</a>, such as the virus that causes COVID-19 and maybe even HIV.</p>
<p>In the meantime, mRNA vaccines may soon <a href="https://doi.org/10.1073/pnas.2217533119">usher in a new era</a> of more effective annual flu vaccines by providing a better match to each flu season’s new variants. <a href="https://www.clinicaltrialsarena.com/features/mrna-vaccine-trials-to-watch/">Two seasonal influenza mRNA vaccines</a> are currently in human clinical trials. If successful, they may offer more effective protection from the annual flu than our current flu vaccines. With mRNA vaccines, I believe that we are at the beginning of starting a new race against flu that we may finally win.</p><img src="https://counter.theconversation.com/content/195807/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Deborah Fuller is a co-founder of Orlance, Inc. a biotechnology company developing a needle-free delivery technology for DNA and RNA vaccine. She also serves as a consultant for HDT Bio, a biotechnology company developing nanoparticle-based formulations to deliver RNA vaccines and Abacus Inc., a therapeutic vaccine company developing B cell targeted therapies for chronic infectious diseases and cancer. She receives grant funding from the National Institutes of Health, the Washington Research Foundation and the Department of Defense.</span></em></p>Annual flu vaccines are in a constant race against a rapidly mutating virus that may one day cause the next pandemic. A one-time vaccine protecting against all variants could give humanity a leg up.Deborah Fuller, Professor of Microbiology, School of Medicine, University of WashingtonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1925672022-12-14T13:14:47Z2022-12-14T13:14:47ZNasal vaccines promise to stop the COVID-19 virus before it gets to the lungs – an immunologist explains how they work<figure><img src="https://images.theconversation.com/files/493959/original/file-20221107-19718-xu583n.jpg?ixlib=rb-1.1.0&rect=0%2C11%2C7360%2C4891&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Nasal vaccines for COVID-19 are still in early development.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/little-cute-blonde-boy-getting-vaccinated-covid-19-royalty-free-image/1282728128?phrase=COVID-19%20nasal%20vaccine&adppopup=true">Paul Biris/Moment via Getty Images</a></span></figcaption></figure><p><em>The Pfizer-BioNTech and Moderna mRNA vaccines have played a large role in preventing deaths and severe infections from COVID-19. But researchers are still in the process of developing alternative approaches to vaccines to improve their effectiveness, including how they’re administered. Immunologist and microbiologist <a href="https://www.researchgate.net/profile/Michael-Russell-10">Michael W. Russell</a> of the University at Buffalo explains how nasal vaccines work, and where they are in the development pipeline.</em></p>
<h2>How does the immune system fight pathogens?</h2>
<p>The immune system has two distinct components: mucosal and circulatory.</p>
<p>The <a href="http://dx.doi.org/10.1016/B978-0-12-415847-4.00001-X">mucosal immune system</a> provides protection at the mucosal surfaces of the body. These include the mouth, eyes, middle ear, the mammary and other glands, and the gastrointestinal, respiratory and urogenital tracts. Antibodies and a variety of other anti-microbial proteins in the <a href="https://theconversation.com/slime-is-all-around-and-inside-you-new-research-on-its-origins-offers-insight-into-genetic-evolution-189278">sticky secretions</a> that cover these surfaces, as well as immune cells located in the lining of these surfaces, directly attack invading pathogens.</p>
<p>The <a href="https://doi.org/10.1186/1741-7007-8-84">circulatory part of the immune system</a> generates antibodies and immune cells that are delivered through the bloodstream to the internal tissues and organs. These circulating antibodies do not usually reach the mucosal surfaces in large enough amounts to be effective. Thus mucosal and circulatory compartments of the immune system are largely <a href="http://dx.doi.org/10.3389/fimmu.2022.957107">separate and independent</a>.</p>
<h2>What are the key players in mucosal immunity?</h2>
<p>The immune components people may be most familiar with are proteins known as <a href="https://www.ncbi.nlm.nih.gov/books/NBK513460/">antibodies, or immunoglobulins</a>. The immune system generates antibodies in response to invading agents that the body identifies as “non-self,” such as viruses and bacteria.</p>
<p>Antibodies bind to specific antigens: the part or product of a pathogen that induces an immune response. Binding to antigens allows antibodies to either inactivate them, as they do with toxins and viruses, or kill bacteria with the help of additional immune proteins or cells.</p>
<p>The mucosal immune system generates a specialized form of antibody called <a href="http://dx.doi.org/10.1038/mi.2011.39">secretory IgA, or SIgA</a>. Because SIgA is located in mucosal secretions, such as saliva, tears, nasal and intestinal secretions, and breast milk, it is resistant to digestive enzymes that readily destroy other forms of antibodies. It is also superior to most other immunoglobulins at neutralizing viruses and toxins, and at preventing bacteria from attaching to and invading the cells lining the surfaces of organs.</p>
<p>There are also many <a href="http://dx.doi.org/10.1002/9780470015902.a0000942.pub2">other key players</a> in the mucosal immune system, including different types of anti-microbial proteins that kill pathogens, as well as immune cells that generate antibody responses.</p>
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<figcaption><span class="caption">Mucus is one of the central secretions of the mucosal immune system.</span></figcaption>
</figure>
<h2>How does the COVID-19 virus enter the body?</h2>
<p>Almost all infectious diseases in people and other animals are <a href="https://www.ncbi.nlm.nih.gov/books/NBK209710/">acquired through mucosal surfaces</a>, such as by eating or drinking, breathing or sexual contact. Major exceptions include infections from wounds, or pathogens delivered by insect or tick bites.</p>
<p>The virus that causes COVID-19, SARS-CoV-2, enters the body via droplets or aerosols that get into your <a href="http://dx.doi.org/10.1038/s41385-020-00359-2">nose, mouth or eyes</a>. It can cause severe disease if it descends deep into the lungs and causes an <a href="https://theconversation.com/long-covid-19-and-other-chronic-respiratory-conditions-after-viral-infections-may-stem-from-an-overactive-immune-response-in-the-lungs-186970">overactive, inflammatory immune response</a>.</p>
<p>This means that the virus’s first contact with the immune system is probably through the surfaces of the nose, mouth and throat. This is supported by the presence of SIgA antibodies against SARS-CoV-2 <a href="http://dx.doi.org/10.3389/fimmu.2020.611337">in the secretions of infected people</a>, including their saliva, nasal fluid and tears. These locations, especially the tonsils, have specialized areas that specifically trigger mucosal immune responses.</p>
<p><a href="http://dx.doi.org/10.3390/pathogens11040397">Some research suggests</a> that if these SIgA antibody responses form as a result of vaccination or prior infection, or occur quickly enough in response to a new infection, they could prevent serious disease by confining the virus to the upper respiratory tract until it is eliminated.</p>
<h2>How do nasal vaccines work?</h2>
<p>Vaccines can be <a href="http://dx.doi.org/10.1016/B978-0-12-415847-4.00055-0">given through mucosal routes</a> via the mouth or nose. This induces an immune response through areas that stimulate the mucosal immune system, leading mucosal secretions to produce SIgA antibodies.</p>
<p>There are <a href="http://dx.doi.org/10.1016/B978-0-12-811924-2.00001-8">several existing mucosal vaccines</a>, most of them taken by mouth. Currently only one, the flu vaccine, is delivered nasally.</p>
<p>In the case of nasal vaccines, the viral antigens intended to stimulate the immune system would be taken up by immune cells within the lining of the nose or tonsils. While the exact mechanisms by which nasal vaccines work in people have not been thoroughly studied, researchers believe they <a href="http://dx.doi.org/10.1007/BF00915547">work analogously to oral mucosal vaccines</a>. Antigens in the vaccine induce B cells in mucosal sites to mature into plasma cells that secrete a form of IgA. That IgA is then transported into mucosal secretions throughout the body, where it becomes SIgA.</p>
<p>If the SIgA antibodies in the nose, mouth or throat target SARS-CoV-2, they could neutralize the virus before it can drop down into the lungs and establish an infection.</p>
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<figcaption><span class="caption">Nasal vaccines could provide a more approachable alternative to injections for patients leery of needles.</span></figcaption>
</figure>
<h2>What advantage do mucosal vaccines have against COVID-19?</h2>
<p>I believe that arguably the best way to protect an individual against COVID-19 is to block the virus at its point of entry, or at least to confine it to the upper respiratory tract, where it might inflict relatively little damage.</p>
<p>Breaking chains of viral transmission is crucial to controlling epidemics. Researchers know that <a href="http://dx.doi.org/10.1093/cid/ciab691">COVID-19 spreads</a> during normal breathing and speech, and is exacerbated by sneezing, coughing, shouting, singing and other forms of exertion. Because these emissions mostly originate from saliva and nasal secretions, where the predominant form of antibody present is SIgA, it stands to reason that secretions with a sufficiently high level of SIgA antibodies against the virus could neutralize and thereby diminish its transmissibility.</p>
<p><a href="http://dx.doi.org/10.3389/fimmu.2022.957107">Existing vaccines</a>, however, do not induce SIgA antibody responses. Injected vaccines primarily induce circulating IgG antibodies, which are effective in preventing serious disease in the lungs. Nasal vaccines specifically induce SIgA antibodies in nasal and salivary secretions, where the virus is initially acquired, and can more effectively prevent transmission.</p>
<p>Nasal vaccines may be a useful supplement to injected vaccines in hot spots of infection. Since they don’t require needles, they might also help overcome vaccine hesitancy due to <a href="https://theconversation.com/over-half-of-adults-unvaccinated-for-covid-19-fear-needles-heres-whats-proven-to-help-161636">fear of injections</a>.</p>
<h2>How close are researchers to creating a nasal COVID-19 vaccine?</h2>
<p>There have been <a href="https://doi.org/10.1038/d41586-022-02824-3">over 100 oral or nasal COVID-19 vaccines in development</a> around the world.</p>
<p>Most of these have been or are currently being tested in animal models. <a href="http://dx.doi.org/10.1126/scitranslmed.abn6868">Many</a> <a href="http://dx.doi.org/10.1126/science.abo2523">have reported</a> successfully inducing protective antibodies in the blood and secretions, and have prevented infection in these animals. However, few have been successfully tested in people. Many <a href="https://www.pharmalive.com/altimmune-to-halt-trials-for-intranasal-covid-19-vaccine">have been abandoned</a> without fully reporting study details.</p>
<p>According to the <a href="https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines">World Health Organization</a>, 14 nasal COVID-19 vaccines are in clinical trials as of late 2022. Reports from <a href="https://doi.org/10.1038/d41586-022-02851-0">China and India</a> indicate that nasal or inhaled vaccines have been approved in these countries. But little information is publicly available about the results of the studies supporting approval of these vaccines.</p><img src="https://counter.theconversation.com/content/192567/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Michael W. Russell receives consultation fees from Therapyx, Inc., and has received previous research grants (now inactive) from the National Institutes of Health; he is also named on current grants to Therapyx, Inc. Therapyx has no interests in products for COVID-19.</span></em></p>An effective nasal vaccine could stop the virus that causes COVID-19 right at its point of entry. But devising one that works has been a challenge for researchers.Michael W. Russell, Professor Emeritus of Microbiology and Immunology, University at BuffaloLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1937052022-11-22T13:25:50Z2022-11-22T13:25:50ZScientists uncovered the structure of the key protein for a future hepatitis C vaccine – here’s how they did it<figure><img src="https://images.theconversation.com/files/496217/original/file-20221118-14-r6a8me.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1999%2C1499&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Imaging the proteins on the surface of HCV has been challenging because of the virus's shape-shifting nature.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/hepatitis-c-virus-particles-illustration-royalty-free-illustration/1042127452">Juan Gaertner/Science Photo Library via Getty Images</a></span></figcaption></figure><p>The <a href="https://www.cdc.gov/hepatitis/hcv/index.htm">hepatitis C virus, or HCV</a>, causes a chronic liver infection that can lead to permanent liver scarring and, in dire cases, cancer. It affects around <a href="https://doi.org/10.1007/s42399-020-00588-3">71 million people worldwide</a> and causes approximately 400,000 deaths each year. While <a href="https://www.uptodate.com/contents/direct-acting-antivirals-for-the-treatment-of-hepatitis-c-virus-infection">treatments are available</a> for HCV-related infections, they are expensive, hard to access and do not protect against reinfection. A vaccine that can help prevent HCV infection is a major unmet medical and public health need. </p>
<p>One major reason there hasn’t been an HCV vaccine yet is that scientists have yet to identify the proper antigen, or the part of the virus would trigger a protective immune response in the body.</p>
<p>Decades of research have pinpointed <a href="https://doi.org/10.1038/nrmicro3098">HCV E1E2</a>, the only protein on the surface of the virus, as the most promising vaccine candidate. However, developing an HCV vaccine based on that protein is limited by uncertainty around what it looks like. Knowing the structure of the protein is necessary to figure out how the immune system responds to the virus.</p>
<p>So how do researchers capture the structure of single protein on a shape-shifting virus? </p>
<p>We are researchers who specialize in <a href="https://scholar.google.com/citations?user=Xejfx54AAAAJ&hl=en">microscopy</a> and <a href="https://scholar.google.com/citations?user=iQj9rSwAAAAJ&hl=en">vaccine design</a>. With new technology, we were able to <a href="https://doi.org/10.1126/science.abn9884">visualize the molecular details</a> of this elusive protein, unlocking key insights into how this virus works and offering a potential blueprint for a future vaccine.</p>
<p>This is how we did it.</p>
<h2>Challenges of capturing a shape-shifting virus</h2>
<p>One reason it has been so difficult to capture the structure of the HCV E1E2 protein is that it is both <a href="https://doi.org/10.1016/j.celrep.2022.110859">flexible and fragile</a>. It changes its shape so often and is so easily broken that it’s challenging to purify. </p>
<p>As an analogy, imagine a bowl of spaghetti drenched in tomato sauce. Now imagine trying to take a picture of each individual piece of spaghetti in the same position over time while the bowl is shaking. Hard to do, right? That’s what it was like to image the full E1E2 protein.</p>
<p>There were also <a href="https://doi.org/10.1126/science.1251652">technological barriers</a>. Until recently, available imaging techniques were limited in their ability to view microscopic proteins. <a href="https://chem.libretexts.org/Bookshelves/Analytical_Chemistry/Supplemental_Modules_(Analytical_Chemistry)/Instrumentation_and_Analysis/Diffraction_Scattering_Techniques/X-ray_Crystallography">X-ray crystallography</a>, for instance, is unable to capture molecules that frequently change and shape-shift, like HCV. Moreover, other options, such as <a href="https://chem.libretexts.org/Bookshelves/Analytical_Chemistry/Physical_Methods_in_Chemistry_and_Nano_Science_(Barron)/04%3A_Chemical_Speciation/4.07%3A_NMR_Spectroscopy">nuclear magnetic resonance spectroscopy</a>, required cutting large parts of the protein or chemically manipulating it in a way that would transform its physiological state and potentially alter its function.</p>
<p>So to examine the structure of E1E2, we needed a way to extract and purify, stabilize and trap the entire shape-shifting protein into one configuration.</p>
<h2>How to take a picture of protein</h2>
<p><a href="https://doi.org/10.1038/d41586-020-01658-1">Cryo-EM, or cryo-electron microscopy</a>, is a type of imaging technique that views specimens at cryogenic temperatures, in this case the boiling point of nitrogen: minus 320.8 degrees Fahrenheit (minus 196 Celsius). With temperatures that cold, ice freezes so quickly that it doesn’t have time to crystallize. That creates a beautiful glasslike frame around the protein of interest, allowing an unhindered view of every structural detail. Cryo-EM also requires very little protein to work, reducing the amount of material we would need to purify. </p>
<p>Winner of the <a href="https://www.nobelprize.org/prizes/chemistry/2017/press-release/">2017 Nobel Prize in chemistry</a> and <a href="https://doi.org/10.1038/nmeth.3730">Nature magazine’s 2015 “Method of the Year</a>” award, cryo-EM is superb for imaging biological macromolecules in their native, or natural, state in the aqueous environment of human blood. Cryo-EM was also pivotal for characterizing the <a href="https://doi.org/10.1038/nature17200">structure of the COVID-19 virus</a> and its variants.</p>
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<figcaption><span class="caption">Cryo-EM has allowed researchers to see complex proteins they weren’t able to before.</span></figcaption>
</figure>
<p>So how do you take a picture of a protein? </p>
<p>First, we embedded the genetic code to make E1E2 in human cells in a petri dish so we would have sufficient amounts of protein to study. After purifying the protein, we <a href="https://caic.bio.cam.ac.uk/electron-microscopy/SpecimenPrep/PlungeFreezing">plunged it into liquid ethane</a> followed by liquid nitrogen. Liquid ethane is used to freeze the protein because it has a higher boiling point than liquid nitrogen. This means it is able to capture more heat before turning to a gas, allowing the protein to freeze much more quickly than it would in liquid nitrogen and avoid structural damage. </p>
<p>Once the protein was vitrified, or in a glasslike ice state, we were able not just to see its overall structure, but also to capture multiple individual configurations of the protein that it takes when it shape-shifts, including its less stable forms.</p>
<p>At this point, our protein was ready for its close-up. We employed a microscope that <a href="https://www.ccber.ucsb.edu/ucsb-natural-history-collections-botanical-plant-anatomy/transmission-electron-microscope">uses a beam of focused, high energy electrons</a> and a very fancy camera that detects how the elections bounce off the protein’s surface. This created a 2D image that we then mathematically transformed into a 3D model. And that was how we got the coveted “close-up” of HCV’s surface protein. </p>
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<figcaption><span class="caption">This video shows the newly identified 3D structure of the E1E2 protein on the surface of the hepatitis C virus. The two main subunits of the protein are colored in pink and blue. Sugar molecules are colored in green.</span></figcaption>
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<p>Our next step was then to assess the location of each amino acid, or building block of the protein, in 3D space. Because every amino acid has a unique shape, we used a computer program that could identify each one in our 3D map. This allowed us to manually reconstruct a high-resolution model of the protein, one building block at a time.</p>
<h2>A new tool to design an HCV vaccine</h2>
<p>Our 3D map and model of the HCV E1E2 protein supports previous research describing its structure while providing new insights into features that will help pave the way for a long-sought vaccine design against this virus. </p>
<p>For example, our structure reveals that the interface between the two main parts of the protein is stabilized by sugars and hydrophobic patches, or areas that push out water molecules. This creates sticky binding hubs along the protein and keeps it from falling apart – a potential site for protective antibodies and new drugs to target. </p>
<p>Researchers now have the tools to design antiviral drugs and vaccines against HCV infection.</p><img src="https://counter.theconversation.com/content/193705/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Lisa Eshun-Wilson receives funding from the National Science Foundation. </span></em></p><p class="fine-print"><em><span>Alba Torrents de la Peña receives funding from Netherlands Organization for Scientific Research (NWO) Rubicon Grant 45219118. </span></em></p>Using a Nobel Prize-winning technique called cryo-EM, researchers were able to identify potential areas on the hepatitis C virus that a vaccine could target.Lisa Eshun-Wilson, Postdoctoral Scholar in Molecular and Cell Biology, The Scripps Research InstituteAlba Torrents de la Peña, Postdoctoral Fellow in Integrative Structural and Computational Biology, The Scripps Research InstituteLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1906012022-09-19T18:01:33Z2022-09-19T18:01:33ZCanadian scientists made life-saving contributions during the COVID-19 pandemic<figure><img src="https://images.theconversation.com/files/485134/original/file-20220916-9898-2fmj80.jpg?ixlib=rb-1.1.0&rect=134%2C0%2C4857%2C2814&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Funding research is essential to meet future health challenges.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><iframe style="width: 100%; height: 100px; border: none; position: relative; z-index: 1;" allowtransparency="" allow="clipboard-read; clipboard-write" src="https://narrations.ad-auris.com/widget/the-conversation-canada/canadian-scientists-made-life-saving-contributions-during-the-covid-19-pandemic" width="100%" height="400"></iframe>
<p>This year, the Nobel Prize in physiology or medicine will be awarded on Oct. 3. Canada will be in the spotlight again, thanks to Canadian scientists’ involvement with mRNA vaccine development. </p>
<p>The Canada Gairdner International Award, offered to five researchers who have excelled in the medical sciences, is often considered a predictor of the Nobel Prize.</p>
<p>Earlier this year, the Gairdner Foundation recognized <a href="https://biochem.ubc.ca/person/pieter-cullis/">molecular biologist Pieter Cullis</a>, <a href="https://www.pennmedicine.org/providers/profile/katalin-kariko">biochemist Katalin Karikó</a> and <a href="https://www.med.upenn.edu/apps/faculty/index.php/g275/p20322">physician-researcher Drew Weissman</a>. Cullis was recognized <a href="https://doi.org/10.1016/j.cell.2022.03.026">for the lipid nanoparticle packaging of the mRNA designed by Karikó and Weissman</a> for the COVID-19 vaccine.</p>
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<figcaption><span class="caption">The 2022 Canada Gairdner International Awards.</span></figcaption>
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<h2>mRNA vaccine development</h2>
<p>Canada’s input into the development of functional mRNA vaccines also includes Nahum Sonenberg, <a href="https://www.mcgill.ca/gci/article/sante-gala-road-rna-therapies">a pioneer of mRNA research</a> who was consulted in the development of Moderna’s mRNA vaccine. Sonenberg received a <a href="https://gairdner.org/award_winners/nahum-sonenberg/">Gairdner International Award in 2008</a> for discovering how mRNA is constructed with a cap and tail to enable protein synthesis. </p>
<p>Moderna was itself co-founded by <a href="https://www.utoronto.ca/news/u-t-alumnus-derrick-rossi-proud-play-role-promising-covid-19-vaccine-toronto-star">Derrick Rossi, who attended the University of Toronto</a>, and <a href="https://mcgillnews.mcgill.ca/s/1762/news/interior.aspx?gid=2&pgid=2347">Noubar Afeyan, who attended McGill University</a>.</p>
<h2>Adenovirus vaccines</h2>
<p>In 2021, in addition to <a href="https://www.canada.ca/en/health-canada/services/drugs-health-products/covid19-industry/drugs-vaccines-treatments/authorization/applications.html">approving the mRNA vaccines from BioNTech and Moderna</a>, Canada also approved the Oxford vaccine. This vaccine uses an adenovirus to insert the gene for the COVID-19 virus spike protein, which stimulates an immune response that protects against COVID-19.</p>
<p><a href="https://brighterworld.mcmaster.ca/articles/analysis-how-the-puzzle-of-viral-vector-vaccines-was-solved-leading-to-todays-covid-19-shots/">Molecular biologist Frank Graham</a> pioneered the use of adenovirus to generate vaccines.</p>
<p>Research has estimated that <a href="https://doi.org/10.1016/S1473-3099(22)00320-6">19.8 million lives were saved by the vaccines in 2021</a>, including over 310,000 lives in Canada alone.</p>
<h2>Undervaluing the importance of research</h2>
<p>The recognition of exceptional scientists by the Nobel Prize committee is sadly not a value shared by our federal government today. In 2017, then <a href="http://www.sciencereview.ca/eic/site/059.nsf/eng/home">Minister of Science Kirsty Duncan</a> highlighted the need for increased funding to the Canadian Institutes of Health Research (CIHR), the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Social Sciences and Humanities Research Council (SSHRC) to reverse the decline in Canadian research. </p>
<p>In 2017, CIHR funding was only 2.5 per cent of that of the corresponding National Institutes of Health (NIH) in the United States. By 2022, CIHR funding was proportionally less, at <a href="https://cihr-irsc.gc.ca/e/52798.html">2.3 per cent</a> of that of the <a href="https://www.aip.org/fyi/2022/nih-budget-fy22-outcomes-and-fy23-request">NIH</a>.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1392118457861386241"}"></div></p>
<p>The U.S. recognizes the importance of research by investing five times more per capita than Canada in health research. As each federal budget is announced, Canadian scientists await eagerly for an increase in budgets to internationally competitive levels which never comes.</p>
<p>The discrepancy between Canada and our peer countries in the G7 and the Organisation for Economic Co-operation and Development means that <a href="https://www.timeshighereducation.com/news/large-surpluses-post-lockdown-blip-say-canadian-universities">our future scientists will look elsewhere for promising, unobstructed careers</a>. </p>
<p>Losing our scientists will have an effect on the health of Canadians and the economy.</p>
<h2>Science literacy</h2>
<p>During the pandemic, Canadians have been following updates and news regarding public health messaging that affects their everyday lives. We have observed and scrutinized how scientific research is conducted and communicated.</p>
<p>The pandemic seems to have sparked a thirst and curiosity for science. The more people inform themselves, the more they are protected from false information which could harm them and their loved ones.</p>
<p>Never has there been a greater need to promote the relevance of science to all across Canada and especially our federal and provincial decision-makers.</p>
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Read more:
<a href="https://theconversation.com/why-cant-canada-win-another-nobel-prize-in-medicine-87910">Why can't Canada win another Nobel Prize in medicine?</a>
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<p>The COVID-19 pandemic opened our eyes to the fact that Canada was unprepared. From the <a href="https://doi.org/10.1038/s41586-020-2012-7">first sequencing of the SARS-CoV-2 viral RNA</a> to the <a href="https://www.england.nhs.uk/2020/12/landmark-moment-as-first-nhs-patient-receives-covid-19-vaccination/">first vaccination</a>, the rapid response from scientists demonstrated why scientific research is so relevant to all. With multiple health threats, investing in research should no longer be seen as a luxury.</p>
<h2>Global competition</h2>
<p>As seemingly uncontrollable inflation and the problems of the hard-hit economy take hold, <a href="https://www.theglobeandmail.com/canada/article-student-scientists-demand-action-on-federal-scholarships/">Canada’s current and future scientists will be gravely affected by the lack of funding to support labs</a>. Without increased investment into scientific research, <a href="https://montrealgazette.com/opinion/opinion-montreal-aids-conference-steeped-in-legacy-and-hope">Canada will not be able to compete scientifically</a>. This plight is a threat to Canada’s health and its economy.</p>
<p>Canada needs to retain, recruit and support talent to meet future challenges. These will come from several sources, including future pandemics, <a href="https://theconversation.com/gutter-to-gut-how-antimicrobial-resistant-microbes-journey-from-environment-to-humans-189446">increased antibiotic resistance to bacterial infections</a>, the growing impact of cancer, age-related diseases and, of course diabetes. Indeed, it was the discovery of insulin that represented <a href="https://www.nobelprize.org/prizes/medicine/1923/summary/">our first Nobel Prize in Physiology or Medicine in 1923</a>.</p>
<p>Research saves lives.</p>
<p><em>John Bergeron gratefully acknowledges Kathleen Dickson as co-author.</em></p><img src="https://counter.theconversation.com/content/190601/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>John Bergeron 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>Canadian scientists have made significant contributions during the pandemic response, including vital roles in developing COVID-19 vaccines. But underfunding puts the future of science in Canada at risk.John Bergeron, Emeritus Robert Reford Professor and Professor of Medicine, McGill UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1895312022-09-04T20:12:33Z2022-09-04T20:12:33ZBetter COVID vaccines are on the way. What do they do? And what technology might we see in future?<figure><img src="https://images.theconversation.com/files/482203/original/file-20220901-20-jcfbtg.jpg?ixlib=rb-1.1.0&rect=80%2C4%2C2775%2C1994&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://unsplash.com/photos/lNkRnZPfiwY">Unsplash/CDC</a></span></figcaption></figure><p>Regulators in <a href="https://www.tga.gov.au/news/media-releases/tga-provisionally-approves-moderna-bivalent-covid-19-vaccine-use-booster-dose-adults">Australia</a> and the <a href="https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-moderna-pfizer-biontech-bivalent-covid-19-vaccines-use">United States</a> last week approved Omicron-specific boosters, following approval in the <a href="https://www.bbc.com/news/health-62548336">United Kingdom</a> in mid-August. </p>
<p>In Australia, a Moderna Omicron booster has been provisionally approved for use in adults aged 18 and over. Supplies are expected to arrive in the <a href="https://www.tga.gov.au/news/media-releases/tga-provisionally-approves-moderna-bivalent-covid-19-vaccine-use-booster-dose-adults">coming weeks</a>, however the Australian Technical Advisory Group on Immunisation (ATAGI) is yet to advise the government on how the vaccine will be used. </p>
<p>So what’s new about the Omicron booster? And what sorts of advances in vaccine technology might we see next?</p>
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Read more:
<a href="https://theconversation.com/covid-vaccine-how-the-new-bivalent-booster-will-target-omicron-188840">COVID vaccine: how the new 'bivalent' booster will target omicron</a>
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<h2>Why do we need new vaccines?</h2>
<p>The current COVID vaccines will go down in history as one of the greatest achievements of medical science. Developed at record pace – without omitting any of the usual steps to ensure safety and efficacy – the vaccines significantly decreased the risk of severe disease and death.</p>
<p>But they’re less effective at reducing infection. Frequent boosters have been required to protect against new sub-variants. This is because the spike protein, which the vaccines target, has changed. And over time, our protection has reduced due to waning immunity. </p>
<h2>What are the Omicron-specific vaccines?</h2>
<p>Most manufacturers of approved COVID vaccines began making boosters targeting previous variants as far back as Alpha. But until Omicron, these variant-specific boosters offered no significant advantage over vaccines targeting the original, or Wuhan, strain. </p>
<p>The new Omicron boosters combine two different targets in the one vaccine, known as a bivalent vaccine. This provides broader cross-protection – against the currently circulating variants but possibly against future variants too. </p>
<p>The first of these boosters, manufactured by Moderna, targets the BA.1 Omicron sub-variant in addition to the original or Wuhan strain. It also provides some protection against BA.4 and BA.5. This is now approved in the <a href="https://www.bbc.com/news/health-62548336">UK</a>, <a href="https://www.tga.gov.au/news/media-releases/tga-provisionally-approves-moderna-bivalent-covid-19-vaccine-use-booster-dose-adults">Australia</a> and <a href="https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-moderna-pfizer-biontech-bivalent-covid-19-vaccines-use">US</a>. </p>
<p>The US has also approved the Pfizer bivalent booster, which <a href="https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-moderna-pfizer-biontech-bivalent-covid-19-vaccines-use">targets</a> the spike of BA.4/BA.5 as well as the original strain.</p>
<h2>What vaccine technology might we see next?</h2>
<p>Scientists are working to develop COVID vaccines that:</p>
<ul>
<li><p>offer longer lasting protection</p></li>
<li><p>protect against new variants and sub-variants </p></li>
<li><p>provide similar levels of protection from a single dose </p></li>
<li><p>don’t require freezing or refrigeration, and that have an extended shelf life</p></li>
<li><p>deliver a strong response from lower doses of active ingredient. </p></li>
</ul>
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<strong>
Read more:
<a href="https://theconversation.com/nose-sprays-needle-free-patches-durable-immunity-towards-the-next-generation-of-covid-vaccines-170861">Nose sprays, needle-free patches, durable immunity: towards the next generation of COVID vaccines</a>
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<p>More than <a href="https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines">120 potential COVID vaccines</a> are in clinical trials. Here are some of the improvements they’re working on.</p>
<p><strong>More robust protection against new variants</strong></p>
<p>Most vaccines approved so far target the entire spike protein. But many vaccines under development specifically target the part of the spike protein that binds to the corresponding receptor on our cells. This is less likely to change than other parts of the spike protein, delivering more robust protection against new variants. </p>
<p>Candidate vaccines using this approach include <a href="https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html?">Icosavax</a> and one from the <a href="https://www.nature.com/articles/s41541-021-00393-6/tables/2">Serum Institute of India</a>. </p>
<p><strong>Easier storage</strong></p>
<p>DNA-based vaccines are similar to mRNA vaccines (Pfizer and Moderna) but are more temperature-stable, making them easier to transport and store. One such vaccine, by manufacturer <a href="https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html?">Zydus</a>, has already received an emergency use authorisation in India and is injected into the skin. Another, by <a href="https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html?">Inovio</a>, is undergoing phase three trials.</p>
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<p><strong>Greater immune responses from lower doses</strong></p>
<p>With current COVID vaccines, the body is given instructions to make the spike protein, or the spike protein itself is delivered. The vaccines cannot replicate or reproduce themselves. Vaccines that can replicate have the potential to generate stronger immune responses or strong enough responses from lower doses. </p>
<p><strong>Variant-proof vaccines</strong></p>
<p>Finally, many vaccines under development have the ambitious target of protecting against all coronviruses or vaccines that are essentially variant-proof. While this has not so far been achieved for any similar family of viruses, there are many promising candidates. </p>
<p>Many rely on combining antigens from many different parts of the virus or even multiple coronaviruses. Others combine multiple receptor-binding domains (potentially allowing the vaccine to give a broader immune response against a range of variants) with other innovative technologies.</p>
<h2>Different routes of administration</h2>
<p>Current vaccines rely on administration via a needle and syringe. This is an issue for people with needle phobias, and presents challenges for the disposal of sharps. So many vaccines <a href="https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines">being developed</a> are given via alternate routes. </p>
<p>One way to deliver vaccines is through the <a href="https://www.theage.com.au/national/nasal-vaccines-could-snuff-out-covid-but-the-hurdles-are-not-to-be-sneezed-at-20220818-p5bars.html">nose</a>, known as intranasal vaccination. Rather than injecting, you breathe it in.</p>
<p>Giving the vaccine via the same route the virus gains entry has the <a href="https://www.science.org/doi/10.1126/sciimmunol.add9947">potential</a> to generate a response that’s better able to stop the virus entering in the first place. </p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1561292777970958336"}"></div></p>
<p>One of the main limitations of nasal vaccines is getting a strong enough immune response to be effective. However there are many promising candidates, including one I’m working on.</p>
<p>Vaccines given via the skin are also a promising area. In addition to the DNA vaccines injected into the skin, others are being developed using vaccine coated onto patches, essentially made of microscopic needles. This is easier to administer.</p>
<p>It may also have some advantages in terms of immune response and its ability to be stored at room temperature. One such vaccine that looks promising has been developed by a group originally from the <a href="https://www.uq.edu.au/news/article/2022/07/covid-vaccine-patch-fights-variants-better-needles">University of Queensland</a>.</p>
<p>Finally, <a href="https://cosmosmagazine.com/health/covid/next-gen-covid-19-vaccines/">oral vaccines</a> you drink are also under development. While potentially the most convenient method of administration, it’s also one that poses great challenges in terms of getting a strong enough response for the required effect. </p>
<p>While up to five vaccines in development are exploring this avenue of administration, including one I’m involved in, they are in relatively early phases of clinical trials.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/a-covid-19-vaccine-may-come-without-a-needle-the-latest-vaccine-to-protect-without-jabbing-146564">A COVID-19 vaccine may come without a needle, the latest vaccine to protect without jabbing</a>
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<img src="https://counter.theconversation.com/content/189531/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Paul Griffin is affiliated with The University of Queensland, Nucleus network and Mater research where he has been the principal investigator on 8 COVID-19 vaccine studies and also serves on the advisory boards of AstraZeneca, MSD, Pfizer (covid therapy) and GSK and has received speaker honoraria from AstraZeneca, Seqirus, Novartis and Gilead</span></em></p>New boosters protect against the original COVID strain as well as Omicron. In future, we might see variant-proof vaccines or those delivered in the nose or mouth.Paul Griffin, Associate Professor, Infectious Diseases and Microbiology, The University of QueenslandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1817722022-06-01T19:29:18Z2022-06-01T19:29:18ZInhaled vaccine for COVID-19: The pandemic accelerated decades of research leading to jab-free vaccine now in human testing<figure><img src="https://images.theconversation.com/files/466340/original/file-20220531-16-inp8qq.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C5000%2C3697&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Inhaled vaccine delivery could take on not only COVID-19, but also other respiratory infections, including tuberculosis.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><iframe style="width: 100%; height: 100px; border: none; position: relative; z-index: 1;" allowtransparency="" allow="clipboard-read; clipboard-write" src="https://narrations.ad-auris.com/widget/the-conversation-canada/inhaled-vaccine-for-covid-19--the-pandemic-accelerated-decades-of-research-leading-to-jab-free-vaccine-now-in-human-testing" width="100%" height="400"></iframe>
<p>No one wanted COVID-19. The pandemic has created misery, death and hardship, and it isn’t finished yet.</p>
<p>Still, the lingering crisis has generated opportunities, by expediting research that may benefit humanity far beyond the pandemic. Inhaled vaccines are one example. I am part of a multidisciplinary team working to make these a practical reality, much sooner than would have been the case without the pandemic.</p>
<figure class="align-right ">
<img alt="A grouping of rod-shaped bacteria coloured orange, against a black background" src="https://images.theconversation.com/files/465937/original/file-20220530-12-e5l8xx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/465937/original/file-20220530-12-e5l8xx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=747&fit=crop&dpr=1 600w, https://images.theconversation.com/files/465937/original/file-20220530-12-e5l8xx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=747&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/465937/original/file-20220530-12-e5l8xx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=747&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/465937/original/file-20220530-12-e5l8xx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=939&fit=crop&dpr=1 754w, https://images.theconversation.com/files/465937/original/file-20220530-12-e5l8xx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=939&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/465937/original/file-20220530-12-e5l8xx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=939&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Magnified image of the bacteria that causes tuberculosis.</span>
<span class="attribution"><span class="source">NIAID</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
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<p>We are now in the early stages of testing a next-generation COVID-19 vaccine that our earlier research in animals suggests will <a href="https://doi.org/10.1016/j.cell.2022.02.005">last longer, be more effective and stand up well to future variants</a> of the COVID-19 virus.</p>
<p>Before COVID-19 emerged, my colleagues and I at McMaster University were working to develop a new inhaled form of vaccine delivery that could finally take on one of the most challenging respiratory infections: tuberculosis, still a scourge in <a href="https://www.who.int/health-topics/tuberculosis#tab=tab_1">low- and middle-income countries</a> and in remote areas. In Canada it <a href="https://www.sac-isc.gc.ca/eng/1570132922208/1570132959826">disproportionately affects people living in Inuit Nunangat and First Nations living on reserve</a>. </p>
<p>After decades of work, progress was steady, but slow. The lack of urgency to solve a problem that mainly affects <a href="https://doi.org/10.1183/09031936.00173608">people living in poor conditions</a> had made it difficult to generate the resources and momentum needed to complete our research.</p>
<h2>The urgency of COVID-19</h2>
<p>The COVID-19 pandemic, being truly global, created the demand for vaccines, such as the now-familiar ones from <a href="https://www.canada.ca/en/health-canada/services/drugs-health-products/covid19-industry/drugs-vaccines-treatments/vaccines.html">Pfizer, Moderna and AstraZeneca</a>. These vaccines have got us through the immediate crisis, as the virus was spreading rapidly, and have served us well, preventing serious illness and death in countries where vaccines were available.</p>
<p>These vaccines represent great strides, but they are <a href="https://doi.org/10.1136/bmj-2021-068632">not as effective in all populations</a>, nor are they as robust <a href="http://doi.org/10.1056/NEJMoa2119451">against new variants</a> as they are against the original strain of SARS-CoV-2, the virus that causes COVID-19.</p>
<p>Our research suggests that the next-generation COVID-19 vaccine we are currently testing will be more effective for longer, and will protect against new variants. </p>
<p>Our team, which includes experts in pathology and molecular medicine, infectious diseases, immunity and aerosol particles, has taken the progress we’d made toward a tuberculosis vaccine and quickly adapted the same approach to COVID-19. This <a href="https://doi.org/10.1172/jci.insight.155655">delivery system can be transformative</a>. </p>
<p>This promising science presents an opportunity to make a lasting and wider impact beyond COVID-19. While we still need to understand more fully how these vaccines work, my colleagues and I are optimistic this will finally give us a step up in controlling tuberculosis and other lung infections. </p>
<h2>An inhaled COVID-19 vaccine</h2>
<p>We are <a href="https://www.cbc.ca/news/canada/hamilton/hamilton-mcmaster-university-inhaled-covid-19-vaccine-1.6276462">conducting human trials</a> of our new COVID-19 vaccine. The Phase 1 clinical study is evaluating safety, as well as testing for evidence of immune responses in the blood and lung. Our new multivalent vaccine, manufactured for our clinical trial in the <a href="https://mirc.mcmaster.ca/research/services/vector-laboratory">Robert E. Fitzhenry Vector Laboratory</a>, targets multiple viral proteins, both the spike protein on the surface and proteins inside the virus. </p>
<p>With new variants, mutations occur in the spike protein on the outside of the virus. This makes the current vaccines less effective because they target only the spike protein. However, other proteins inside the virus stay the same. <a href="https://brighterworld.mcmaster.ca/articles/researchers-to-begin-human-trials-for-promising-new-inhaled-covid-19-vaccines-designed-to-combat-variants-of-concern/">Targeting multiple proteins means that if clinical trials show that our multivalent COVID vaccine</a> is effective, it will still protect against infection with new variants as they come along. </p>
<figure>
<iframe src="https://player.vimeo.com/video/652221887" width="500" height="281" frameborder="0" webkitallowfullscreen="" mozallowfullscreen="" allowfullscreen=""></iframe>
<figcaption><span class="caption">McMaster University video explaining how the new vaccine would be delivered by aerosol inhalation directly into the lungs.</span></figcaption>
</figure>
<p>In addition to being a friendlier way to take a vaccine, the inhaled form requires much less vaccine — as little as one per cent of what is currently being used in the present vaccines.</p>
<p>The new process delivers the vaccine directly to where the body will use it: the mucosal surface of the airways. This means <a href="https://doi.org/10.1016/j.cell.2022.02.005">less waste and more benefit, lower costs and reduced side-effects</a>.</p>
<p>The vaccine triggers an immune response in the cells lining the lungs to directly protect against COVID-19. This mucosal vaccination could also protect against other respiratory infections, from the common cold to influenza and bacterial pneumonia by rapidly calling on a range of immune cells that are at the ready as the first line of defence against infection. This lasting and broad form of general protection against infection is called <a href="https://ciiid.washington.edu/content/what-innate-immunity">innate immunity</a>. </p>
<p>When the virus particles in the vaccine are taken up by immune cells in the lung, they recruit more cells from elsewhere in the body and together they generate a strong immune response. The process involves a very beneficial type of cell called memory T cells, which, once recruited and activated, stay in the lung, and remain ready to face the infection. </p>
<h2>Decades of research</h2>
<p>Our <a href="https://globalnexus.mcmaster.ca/impact-areas/vaccine-innovation-roll-out/">multidisciplinary team</a> has arrived at the threshold of introducing this potentially transformative vaccine by pivoting decades of research. The antecedent of this work, the development of the viral vector, dates back more than 50 years to <a href="https://theconversation.com/how-the-puzzle-of-viral-vector-vaccines-was-solved-leading-to-todays-covid-19-shots-167341">the work of molecular biologist Frank Graham</a>, who created a microscopic Trojan horse by using a human adenovirus to carry critical viral genes safely into the body.</p>
<p>If we are able to show the new inhaled vaccine is safe and effective, as we anticipate, the payoffs can be huge in terms of human health, medical costs and better quality of life overall, especially for vulnerable populations. We are hopeful that greatly reduced costs for production, storage and shipping of the new vaccine product will allow greater access in developing and remote areas.</p>
<p>No one wanted this pandemic, but when at last it’s over, a new generation of vaccines targeting lung infections means we may all be able to breathe again, in all senses of the expression.</p><img src="https://counter.theconversation.com/content/181772/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Fiona Smaill receives funding from:.
Canadian Institutes of Health Research </span></em></p>An inhaled COVID-19 vaccine would go directly to where the body would use it: the mucosal surface of the airways. This could mean less waste and more benefit, lower costs and reduced side-effects.Fiona Smaill, Professor of Pathology and Molecular Medicine, McMaster UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1621302021-06-28T10:46:59Z2021-06-28T10:46:59ZCOVID vaccine trials were a triumph – now we need a similar system for antibiotics<figure><img src="https://images.theconversation.com/files/406974/original/file-20210617-17-850ilu.jpeg?ixlib=rb-1.1.0&rect=458%2C44%2C2523%2C1491&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/clinical-trial-medicine-covid19-coronavirus-on-1725758620">Shutterstock/ScottCornell</a></span></figcaption></figure><p>The triumph of COVID-19 vaccine development and the discovery of effective treatments was only possible because of the unprecedented coordination of clinical trials. A process of testing – that often lasts over a decade – was compressed into <a href="https://www.nature.com/articles/d41586-020-03626-1">less than nine months</a>. This should now be the model for other major planetary health crises – namely, antimicrobial resistance (AMR).</p>
<p>To stay ahead of, and rapidly respond to, non-viral microbial threats, we believe it is time for a new forward-looking clinical trials infrastructure. A network of public clinical trials institutes could permanently connect pre-clinical academic ingenuity with the best of post-clinical commercial savvy and replenish the empty pipeline for new antibiotics. Action is urgently needed. That was the conclusion of <a href="https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(21)00182-8/fulltext">a study</a> we conducted with <a href="https://www.lstmed.ac.uk/about/people/dr-adam-roberts">Adam Roberts</a>, at the Liverpool School of Tropical Medicine, and <a href="https://www.ceh.ac.uk/staff/andrew-singer">Andrew Singer</a>, at the UK Centre for Ecology and Hydrology.</p>
<p>AMR – the natural process whereby bacteria adapt to resist the antibiotics used to control them – poses a grave threat to <a href="https://gh.bmj.com/content/5/9/e003091">global health and food production systems</a>. Tens of thousands <a href="https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf">of people</a> are already dying and many more are suffering from infections that were once treatable, and the problem is <a href="https://resistancemap.cddep.org/index.php">growing quickly</a>.</p>
<p>Part of the solution lies in taking better care of the antibiotics we already have at our disposal. Every time an antibiotic is used, it creates an <a href="https://microbiologysociety.org/publication/briefing/antimicrobial-resistance-explainer.html">evolutionary advantage</a> for bacteria that can withstand its effects. Over time, this leads to a resistant bacterial population. So antibiotics are a time-limited resource that must be used sparingly. </p>
<p>Bacteria have evolved resistance to <a href="https://www.gov.uk/government/publications/health-matters-antimicrobial-resistance/health-matters-antimicrobial-resistance">every antibiotic</a> ever developed. For example, it took just <a href="https://theconversation.com/why-resistance-is-common-in-antibiotics-but-rare-in-vaccines-152647">six years</a> for resistance to penicillin, the first antibiotic, to become widespread in British hospitals.</p>
<figure class="align-center ">
<img alt="A man wearing facemask getting a COVID vaccine." src="https://images.theconversation.com/files/406980/original/file-20210617-27-1r4d9gy.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/406980/original/file-20210617-27-1r4d9gy.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/406980/original/file-20210617-27-1r4d9gy.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/406980/original/file-20210617-27-1r4d9gy.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/406980/original/file-20210617-27-1r4d9gy.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/406980/original/file-20210617-27-1r4d9gy.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/406980/original/file-20210617-27-1r4d9gy.jpeg?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">
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<span class="caption">Vaccination centre in the Netherlands providing Pfizer jabs in April, 2021.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/helmond-netherlands-april-24-2021-man-1962480328">Shutterstock/NicolasEconomou</a></span>
</figcaption>
</figure>
<p>The other part of the solution lies in stimulating the antibiotic research and development pipeline for <a href="https://www.pewtrusts.org/en/research-and-analysis/issue-briefs/2020/04/tracking-the-global-pipeline-of-antibiotics-in-development">new antibiotics</a>. </p>
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Read more:
<a href="https://theconversation.com/scientists-around-the-world-are-already-fighting-the-next-pandemic-115246">Scientists around the world are already fighting the next pandemic</a>
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<h2>Luring investors</h2>
<p>But there are <a href="https://www.reactgroup.org/wp-content/uploads/2021/03/ReAct-Report-Ensuring-sustainable-access-to-effective-antibiotics-for-everyone-everywhere-How-to-address-the-global-crisis-in-antibiotic-Research-and-Development-March-2021.pdf">well-known</a> economic barriers to commercial antibiotic research and development. The most important is that research, trials and licensing of new drugs is expensive – but new antibiotics yield less profit than drugs for cancer or chronic conditions and need to be protected from overuse to prevent resistance. </p>
<p>There is also no guarantee that investing in a promising compound that was discovered during pre-clinical research will translate into a viable drug. Currently, around 95% of promising pre-clinical compounds that enter human trials do not make it through the so-called “<a href="https://transmedcomms.biomedcentral.com/articles/10.1186/s41231-019-0050-7">valley of death</a>” of clinical trials to regulatory approval.</p>
<p>This is because some compounds show little or no effect, others have side-effects, and some developers are unable to attract and sustain the levels of investment that are necessary to finance expensive clinical trials, which can take over 13 years. Many more research projects fail before they even get tested in humans.</p>
<p>Faced with so many risks and less attractive profit outlooks than with other drugs, why would any commercial developer invest in antibiotic research?</p>
<p>To lure commercial investors back into the fold, Britain, the US and the EU have invested more than US$1.5 billion of public money to subsidise early-stage research and increase the financial yield of antibiotics that <a href="https://linkinghub.elsevier.com/retrieve/pii/S1473-3099(19)30552-3">make it through trials</a>. </p>
<p>At the recent G7 meeting, the UK <a href="https://rstmh.org/news-blog/blog/amr-is-at-the-g7-lessons-from-covid-19">tried to promote</a> a so-called antibiotic subscription model, which it had implemented in 2020. Similar to Netflix, governments would no longer pay industry per antibiotic pill used (as they do now) but for the value of that pill to society. It is hoped that guaranteed profits and minimised investment risks will entice large pharmaceutical companies to reinvest in research and development. </p>
<p>So far, the success of traditional market-centred subsidies <a href="https://wellcomeopenresearch.org/articles/6-146">has been limited</a> and G7 members did not explicitly commit to the UK subscription model. Although they did agree to explore further strengthening of <a href="https://www.gov.uk/government/publications/g7-finance-ministers-meeting-june-2021-communique/g7-finance-ministers-and-central-bank-governors-communique">market incentives</a>. </p>
<h2>Learning from COVID-19</h2>
<p>With a global surge of antimicrobial-resistant organisms <a href="https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance">already upon us</a> and COVID-19 placing <a href="https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(21)00090-2/fulltext">further pressure</a> on existing antibiotics as a result of co- and secondary infections, we urgently need new creative approaches to refilling the pipeline.</p>
<p>One solution may be to turn the existing subsidy model for new antibiotics on its head. Rather than putting all eggs in one basket and funding individual companies with drugs that may or may not make it through the valley of death, we propose building a bridge to cross this valley with a network of public institutes. These institutes would be capable of carrying out clinical trials and producing limited amounts of experimental antibiotics. They could essentially fix the broken pipeline.</p>
<p>A dedicated antibiotic clinical trials infrastructure would combine the best of public and private sector knowhow. Intellectual property resulting from public research would stay in the public’s hands and academics could take <a href="https://www.pnas.org/content/111/18/6542">full credit</a> for their discoveries by publishing results rather than waiting for patent applications to be filed.</p>
<figure class="align-center ">
<img alt="Hand holding a petri dish containing bacteria." src="https://images.theconversation.com/files/406983/original/file-20210617-16-1x1be80.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/406983/original/file-20210617-16-1x1be80.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=627&fit=crop&dpr=1 600w, https://images.theconversation.com/files/406983/original/file-20210617-16-1x1be80.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=627&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/406983/original/file-20210617-16-1x1be80.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=627&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/406983/original/file-20210617-16-1x1be80.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=788&fit=crop&dpr=1 754w, https://images.theconversation.com/files/406983/original/file-20210617-16-1x1be80.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=788&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/406983/original/file-20210617-16-1x1be80.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=788&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Antimicrobial susceptibility testing in petri dish.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/antimicrobial-susceptibility-testing-petri-dish-antibiotic-1887881980">Shutterstock/Saiful52</a></span>
</figcaption>
</figure>
<p>In addition to protecting compounds from commercial failure and disappearing behind patent barriers, a permanent network of clinical trial institutes could also decrease the cost and increase the quality of the trials.</p>
<p>At the moment, developers have to attract large amounts of venture capital to fund commercial trials. Dedicated antibiotic trials institutes would de-risk this process, build human expertise in trialling drugs and significantly lower research and development costs for public and private developers.</p>
<p>By making access to public trials networks dependent on targeting <a href="https://www.who.int/medicines/areas/rational_use/PPLreport_2017_09_19.pdf?ua=1">priority pathogens identified by the World Health Organization</a>, pre-clinical research and development would be incentivised to target the most pressing and – not just the most profitable – health issues. Meanwhile, clinical trials could take place in the low-income areas where new antibiotics are most needed.</p>
<p>At the end of a clinical trial, industry could be commissioned to do what it does best: manufacture and distribute. Similar to other public services provided by for-profit companies, new drugs could be distributed by commercial manufacturers capable of guaranteeing environmentally sound production and accessible drug prices.</p>
<p>Long-term supply contracts for healthcare providers and a repurposing of existing antibiotic subscription models in the UK and Sweden could easily be used to entice bidding by manufacturers and guarantee commercially viable production of new drugs.</p>
<p>The global COVID vaccine response has revealed the importance of forward-looking public infrastructure and research investment to stay ahead of and rapidly respond to microbial threats. </p>
<p>A network of public clinical trials institutes for antibiotics could do just that and benefit both public and commercial developers in the process. After over 30 years of <a href="https://www.nature.com/articles/d41586-020-02884-3">stalling innovation</a> and stop-start subsidies, this could permanently bridge the trials gap.</p>
<hr>
<p><em>This article is part of a series on recovering from the pandemic in a way that makes societies more resilient and able to deal with future challenges. Read more of the coverage <a href="https://theconversation.com/uk/topics/resilient-recovery-series-106366">here</a>.</em></p><img src="https://counter.theconversation.com/content/162130/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Claas Kirchhelle receives funding from the Wellcome Trust.
</span></em></p><p class="fine-print"><em><span>Rebecca Glover is funded by the NIHR Policy Research
Program through its core support to the Policy Innovation and Evaluation
Research Unit (Project No: PR-PRU-1217-20602). The views expressed
are those of the author(s) and are not necessarily those of the NIHR or
the Department of Health and Social Care</span></em></p>A new network of public clinical trials institutes is urgently needed to replenish the empty pipeline for new antibiotics.Claas Kirchhelle, Lecturer in the History of Medicine, University College DublinRebecca Glover, Research Fellow, Health Services Research and Policy, London School of Hygiene & Tropical MedicineLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1603852021-05-07T13:39:21Z2021-05-07T13:39:21ZCOVID vaccine weekly: support builds for patent waiver as shortages threaten to bite<figure><img src="https://images.theconversation.com/files/399295/original/file-20210506-17-tt8tzt.jpg?ixlib=rb-1.1.0&rect=293%2C185%2C4707%2C3194&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.alamy.com/washington-dc-usa-march-11-2021-pictured-protesters-holding-a-banner-in-front-of-the-phrma-office-during-the-free-the-vaccine-protest-demonstrators-called-on-phrma-the-industry-group-for-pharmaceuticals-to-agree-to-the-wto-trips-waiver-and-make-the-coronavirus-vaccine-available-patent-free-to-developing-countries-credit-allison-c-baileyalamy-live-news-image414588256.html?pv=1&stamp=2&imageid=02F53BA9-AA3E-4B7B-8C08-27420EDA5525&p=1253258&n=8&orientation=0&pn=1&searchtype=0&IsFromSearch=1&srch=foo%3Dbar%26st%3D0%26sortby%3D2%26qt%3Dtrips%2520waiver%26qt_raw%3Dtrips%2520waiver%26qn%3D%26lic%3D3%26edrf%3D0%26mr%3D0%26pr%3D0%26aoa%3D1%26creative%3D%26videos%3D%26nu%3D%26ccc%3D%26bespoke%3D%26apalib%3D%26ag%3D0%26hc%3D0%26et%3D0x000000000000000000000%26vp%3D0%26loc%3D0%26ot%3D0%26imgt%3D0%26dtfr%3D%26dtto%3D%26size%3D0xFF%26blackwhite%3D%26cutout%3D%26archive%3D1%26name%3D%26groupid%3D%26pseudoid%3D%26userid%3D%26id%3D%26a%3D%26xstx%3D0%26cbstore%3D1%26resultview%3DsortbyPopular%26lightbox%3D%26gname%3D%26gtype%3D%26apalic%3D%26tbar%3D1%26pc%3D%26simid%3D%26cap%3D1%26customgeoip%3DGB%26vd%3D0%26cid%3D%26pe%3D%26so%3D%26lb%3D%26pl%3D0%26plno%3D%26fi%3D0%26langcode%3Den%26upl%3D0%26cufr%3D%26cuto%3D%26howler%3D%26cvrem%3D0%26cvtype%3D0%26cvloc%3D0%26cl%3D0%26upfr%3D%26upto%3D%26primcat%3D%26seccat%3D%26cvcategory%3D*%26restriction%3D%26random%3D%26ispremium%3D1%26flip%3D0%26contributorqt%3D%26plgalleryno%3D%26plpublic%3D0%26viewaspublic%3D0%26isplcurate%3D0%26imageurl%3D%26saveQry%3D%26editorial%3D%26t%3D0%26filters%3D0"> Allison Bailey/Alamy</a></span></figcaption></figure><p>The US has this week backed a proposal to allow countries to manufacture COVID-19 vaccine doses without needing the agreement of the vaccines’ rights holders. This would be enabled by temporarily waiving intellectual property (IP) protection on all COVID-19 medical products. Removing such protections, the waiver’s proponents argue, will increase the amount of vaccine doses produced globally.</p>
<p>This is the theory. But in practice, waiving IP is unlikely to be a short-term solution to increasing vaccine manufacture, <a href="https://theconversation.com/covid-vaccines-why-waiving-patents-wont-fix-global-shortage-scientist-explains-158643">argues</a> Anne Moore, senior lecturer in biochemistry and cell biology at University College Cork. Skills, knowledge and equipment will need to be shared and developed at new sites, which takes time, and material shortages are already limiting production. </p>
<p>Not only that, but IP plays a key role in making sure that vaccines get sufficient industrial backing to be developed in the first place. If protection is waived in the face of a public emergency, even as a one-off, will firms invest next time there is a similar emergency, <a href="https://theconversation.com/us-backed-vaccine-patent-waiver-pros-and-cons-explained-160480">asks</a> Farasat Bokhari,
senior lecturer in economics at the University of East Anglia. Undermining IP could make it harder to respond quickly and effectively to diseases in the future. </p>
<hr>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/320716/original/file-20200316-18073-ruhw8b.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/320716/original/file-20200316-18073-ruhw8b.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/320716/original/file-20200316-18073-ruhw8b.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/320716/original/file-20200316-18073-ruhw8b.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/320716/original/file-20200316-18073-ruhw8b.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/320716/original/file-20200316-18073-ruhw8b.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/320716/original/file-20200316-18073-ruhw8b.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">
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<p><em><strong>This is our weekly round-up of expert information about the <a href="https://theconversation.com/uk/topics/covid-vaccines-96571">COVID-19 vaccines</a>.</strong> <br>
The Conversation, a not-for-profit group, works with a wide range of academics across its global network to produce evidence-based analysis and insights. Get more regular updates from trusted experts by <a href="https://theconversation.com/uk/newsletters/the-daily-2">subscribing to our free newsletter</a> .</em></p>
<hr>
<p>In the meantime, Cuba is in a race to make its own COVID-19 vaccine, as explained in the <a href="https://theconversation.com/cubas-race-to-make-its-own-coronavirus-vaccine-podcast-160324">latest episode</a> of The Conversation Weekly podcast. Its efforts are an alternative approach to the same problem identified by those behind the IP waiver, argues Peter Hotez of Baylor College of Medicine in the US – namely, how to avoid low- and middle-income countries being wholly dependent on multinational companies for the vaccines they need.</p>
<p>Cuba has five vaccine candidates in development, two of which have reached phase 3 trials and are being rolled out to thousands of healthcare workers. In the west, widespread distribution of a medical products that haven’t completed testing would be a cause for alarm, but in Cuba, “trust in the government in regards to healthcare has been built up through many, many decades”, explains Jennifer Hosek of Queen’s University, Ontario in Canada.</p>
<p>Certainly, the current situation suggests the world’s vaccine-production capacity needs to be expanded. Much of the world is reliant on Covax, the vaccine-sharing programme, for COVID-19 vaccine doses, with India a key supplier. The risks of relying so heavily on one source are now being realised, <a href="https://theconversation.com/what-indias-second-wave-means-for-its-vaccine-coverage-and-the-rest-of-the-world-159937">writes</a> Rory Horner, senior lecturer at the University of Manchester’s Global Development Institute. Vaccine production in India is struggling, while its second wave means doses intended for export are instead being used for domestic vaccination programmes. The result is that many countries are now short of expected supplies.</p>
<p>Indeed, India’s second wave is still getting worse. New cases have now breached <a href="https://www.bbc.co.uk/news/world-asia-india-56961940">400,000</a> a day, with daily deaths close to exceeding <a href="https://www.washingtonpost.com/nation/2021/05/06/coronavirus-covid-live-updates-us/">4,000</a>. Yet only <a href="https://ourworldindata.org/explorers/coronavirus-data-explorer?zoomToSelection=true&pickerSort=desc&pickerMetric=population&Metric=People+vaccinated&Interval=Cumulative&Relative+to+Population=true&Align+outbreaks=false&country=%7EIND">around 10%</a> of the population has received a COVID-19 vaccine dose, even despite export doses being redirected internally. It’s time, therefore, for rich nations with good coverage to start donating vaccines to countries, like India, that are clearly in need, <a href="https://theconversation.com/oxford-vaccine-professor-rich-countries-have-a-moral-duty-to-share-their-covid-19-shots-160116">says</a> Andrew Pollard, director of the Oxford Vaccine Group. Not only do they have a moral duty to help the vulnerable, but spreading coverage more widely will suppress the virus and return the world to normality more quickly.</p>
<hr>
<p><em>Get the latest news and advice on <a href="https://theconversation.com/uk/covid-19">COVID-19</a>, direct from the experts in your inbox. Join hundreds of thousands who trust experts by <strong><a href="https://theconversation.com/uk/newsletters/the-daily-2">subscribing to our newsletter</a></strong>.</em></p><img src="https://counter.theconversation.com/content/160385/count.gif" alt="The Conversation" width="1" height="1" />
Various strategies are being pursued to boost worldwide vaccine coverage.Rob Reddick, Commissioning Editor, COVID-19Licensed 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>
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</em>
</p>
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<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>
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</em>
</p>
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<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>
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<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>
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</p>
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<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>
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<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/1586432021-05-04T12:38:01Z2021-05-04T12:38:01ZCOVID vaccines: why waiving patents won’t fix global shortage – scientist explains<figure><img src="https://images.theconversation.com/files/397841/original/file-20210429-18-vgiwlm.jpg?ixlib=rb-1.1.0&rect=498%2C114%2C4299%2C2636&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/two-engineers-scientists-technicians-sterile-cleanroom-782843017">Gorodenkoff/Shutterstock</a></span></figcaption></figure><p>COVID-19 vaccines are key to ending the pandemic. From a humanitarian, moral and pragmatic perspective, the countries must unite to ensure fair and rapid access to these vaccines, worldwide. As <a href="https://www.who.int/news-room/commentaries/detail/a-global-pandemic-requires-a-world-effort-to-end-it-none-of-us-will-be-safe-until-everyone-is-safe">political</a> and <a href="https://www.gavi.org/vaccineswork/why-no-one-safe-until-everyone-safe-during-pandemic">health</a> leaders have stressed: <a href="https://www.theguardian.com/world/2021/jan/31/jeremy-farrar-until-we-are-all-safe-no-one-is-safe-covid-is-a-global-problem">no one is safe until we are all safe</a>.</p>
<p>But satisfying this need is complicated. Before the pandemic, the global demand for all vaccines was around <a href="https://www.who.int/immunization/programmes_systems/procurement/mi4a/platform/module2/2020_Global_Vaccine_Market_Report.pdf?ua=1">5.5 billion doses</a> a year. We now need at least three times this for COVID-19 alone, with continued high-scale production likely to be needed in subsequent years.</p>
<p>Such a fast increase in vaccine production is unprecedented and expected obstacles need to be addressed. One particular idea gaining traction is that vaccine production is being limited by patents and other intellectual property (IP) rights – legal mechanisms that allow organisations to stop others (for a limited period) from making, using or selling their inventions without their permission – and that these should be waived. This, however, should not be a major priority.</p>
<h2>Not the main barrier</h2>
<p>South Africa and India have <a href="https://docs.wto.org/dol2fe/Pages/SS/directdoc.aspx?filename=q:/IP/C/W669.pdf&Open=True">petitioned</a> the World Trade Organization (WTO) to waive certain IP protections, for a limited time, that relate to products for preventing, containing or treating COVID-19. This would allow countries to produce COVID-related products, such as vaccines, for themselves, <a href="https://theconversation.com/intellectual-property-and-covid-19-medicines-why-a-wto-waiver-may-not-be-enough-155920">without fear</a> of being punished for infringing the IP rights of the companies that developed them. </p>
<p>Various NGOs, former heads of state and Nobel laureates have <a href="https://peoplesvaccinealliance.medium.com/open-letter-former-heads-of-state-and-nobel-laureates-call-on-president-biden-to-waive-e0589edd5704">declared their support</a>. It’s <a href="https://www.unaids.org/en/resources/presscentre/featurestories/2021/april/20210414_letter-waive-intellectual-property-rules-COVID-vaccines">claimed</a> that waiving IP agreements “would expand global manufacturing capacity”, allowing production to ramp up “unhindered by industry monopolies that are driving the dire supply shortages blocking vaccine access”.</p>
<p>The WTO petition <a href="https://www.bloomberg.com/news/articles/2020-03-20/world-war-ii-style-production-may-%20carry-legal-risks-for-patriots">references</a> <a href="https://eu.courier-journal.com/story/news/2020/04/03/beshear-calls-3-m-%20release-patent-n-95-respirator-amid-pandemic/5112729002/">suggestions</a> that IP rights have limited the availability of personal protective equipment and the production of ventilators during the pandemic. However, little (if any) evidence has been presented that suggests IP protection is blocking COVID-19 vaccine manufacture.</p>
<p>Rather, technical and logistic issues are the biggest barriers currently standing in the way of increasing vaccine production and deployment. To boost vaccine availability right now, it would be better to address these.</p>
<p>One obstacle to increasing production is the <a href="https://www.businesstoday.in/current/economy-politics/not-just-serum-shortage-of-vaccine-raw-material-troubling-global-vaccine-makers/story/433506.html">supply of raw materials</a> needed to make and deploy these vaccines. The almost instantaneous tripling of demand for specialised materials is placing <a href="https://www.cidrap.umn.edu/news-perspective/2021/03/officials-explore-covid-vaccine-supply-gaps-boosting-production">huge pressure</a> on many pharmaceutical and medical supply chains. This needs to be fixed, not just to help with the production of <a href="https://theconversation.com/the-world-is-hungry-for-mrna-covid-vaccines-like-pfizers-but-were-short-of-vital-components-159143">authorised COVID-19 vaccines</a>, but also to ensure we don’t delay testing and approving vaccines still in development.</p>
<figure class="align-center ">
<img alt="Empty glass vaccine vials" src="https://images.theconversation.com/files/397822/original/file-20210429-21-11im793.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/397822/original/file-20210429-21-11im793.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/397822/original/file-20210429-21-11im793.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/397822/original/file-20210429-21-11im793.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/397822/original/file-20210429-21-11im793.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/397822/original/file-20210429-21-11im793.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/397822/original/file-20210429-21-11im793.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">
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<span class="caption">There have been shortages of glass vials and stoppers because of the sharp increase in vaccine producton.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/glass-vials-liquid-samples-laboratory-equipment-488556421">Nordroden/Shutterstock</a></span>
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<p>Second, transferring the manufacturing process from one facility to another always takes significant resources, as staff at the new site need to be trained in every aspect of production and quality assurance. On top of this, skills are also required in the clinical, legal, commercial and regulatory aspects. Expanding production capacity is thus not instantaneous, and certainly wouldn’t immediately happen just because IP protection has been waived.</p>
<p>Nevertheless, this technology transfer continues, with several COVID-19 vaccine manufacturers transferring their technology, under licence, to sub-contractors. An example is the licensing of the AstraZeneca vaccine to the <a href="https://www.theguardian.com/global-development/2021/feb/14/we-took-a-huge-risk-the-indian-firm-making-more-covid-jabs-than-anyone">Serum Institute of India</a>. To get manufacturing going, the institute dedicated 1,000 staff to the project. </p>
<p>This raises a further point, which is that for technology transfer to work, countries must have specialised facilities and a skilled workforce capable of making vaccines. They also need robust regulatory authorities to audit and approve the safety of what’s produced. </p>
<p>Advocating for current and long-term commitments to increasing these skills around the world could be a more successful way of increasing the number of countries manufacturing vaccines in the long term, compared to waiving IP rights. Indeed, past efforts to increase worldwide manufacturing capacity and access for other medicines, <a href="https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwiFw4T616PwAhWVQhUIHYVND4kQFjACegQIBBAD&url=https%3A%2F%2Feuropa.eu%2Fcapacity4dev%2Ffile%2F22470%2Fdownload%3Ftoken%3DOGn_hfs3&usg=AOvVaw2PxlEmDbZbxQiiBvWsj7pj">such as those for drug-resistant tuberculosis</a>, have taken this sort of broader approach and not focused solely on IP.</p>
<p>Likewise, if we are serious about improving access to COVID-19 vaccines, other issues need to be addressed. Pricing, as well as allocation and deployment mechanisms, such as Covax, <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00306-8/fulltext">must be optimised</a> to allow equitable vaccine deployment.</p>
<h2>IP remains useful</h2>
<p>Love it or loathe it, IP also plays a central role in getting vaccines developed.</p>
<p>Given the emergency we’re in, companies that are normally competitors are <a href="https://www.biopharmadive.com/news/novartis-pfizer-biontech-cororonavirus-vaccine-supply-deal/594215/">working together to produce vaccines</a>. Here, IP can facilitate cooperation; it’s clear which organisation owns what technology, meaning companies don’t have to worry about their ideas being taken when collaborating.</p>
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<img alt="A technician at work in a lab developing vaccines" src="https://images.theconversation.com/files/397823/original/file-20210429-22-gykcew.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/397823/original/file-20210429-22-gykcew.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=337&fit=crop&dpr=1 600w, https://images.theconversation.com/files/397823/original/file-20210429-22-gykcew.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=337&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/397823/original/file-20210429-22-gykcew.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=337&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/397823/original/file-20210429-22-gykcew.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/397823/original/file-20210429-22-gykcew.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/397823/original/file-20210429-22-gykcew.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">
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<span class="caption">IP protection removes worries that might arise when working with other companies.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/shot-sterile-pharmaceutical-manufacturing-laboratory-where-1268263657">Gorodenkoff/Shutterstock</a></span>
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<p>Plus, for academics who aim to translate their research into having real-world impact, there are few options other than to license their innovations to commercial entities who have the expertise and resources to bring the research into clinical use. The COVID-19 vaccine partnership between the University of Oxford and AstraZeneca is a successful example of this inter-dependency.</p>
<p>Such transactional agreements (and so developing health innovations from academic research) rely on IP and being able to give commercial partners exclusive access to knowledge. Enacting an IP waiver risks bringing levels of uncertainty across the vaccine field because, without the exclusive rights to a product, it’s less clear if developing it will lead to a return on investment.</p>
<p>This may put companies off working on vaccines. The vaccine space has only recently grown from being a very narrow field, comprising just a few companies at the <a href="https://www.healthaffairs.org/doi/pdf/10.1377/hlthaff.24.3.622">start of the century</a>, so the threat of losing developers is real. We need to have as many competitors in the field as possible to sustain diverse academic-commercial partnerships. This diversity has already helped create a range of COVID-19 vaccines. </p>
<p>Current IP regulations are not perfect, and this IP waiver discussion rightly forces an examination of current systems. However, waiving IP is unlikely to be a short-term solution to rapid vaccine manufacture and deployment and could lead to long-term obstacles for vaccine development.</p><img src="https://counter.theconversation.com/content/158643/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Anne Moore has previously received funding from Irish and EU funding bodies and has performed research in collaboration with, and under contract for, small-sized vaccine companies. She has filed a number of patents relating to vaccines, vaccine delivery systems and drug delivery systems. </span></em></p>Increasing skills and the availability of raw materials would be a bigger boost for vaccine production right now.Anne Moore, Senior Lecturer in Biochemistry and Cell Biology, University College CorkLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1591432021-04-27T20:06:09Z2021-04-27T20:06:09ZThe world is hungry for mRNA COVID vaccines like Pfizer’s. But we’re short of vital components<p>Given the AstraZeneca COVID-19 vaccine is no longer recommended for under-50s following news of very rare <a href="https://theconversation.com/what-is-thrombocytopenia-the-rare-blood-condition-possibly-linked-to-the-astrazeneca-vaccine-158522">blood clots</a>, Australia is looking to other vaccines to plug the gap.</p>
<p>Pfizer’s mRNA vaccine will become the mainstay of the rollout, with <a href="https://www.abc.net.au/news/2021-04-09/national-cabinet-astrazeneca-covid-vaccine-clots-rollout/100058440">40 million doses</a> expected to arrive before year’s end.</p>
<p>But Australia isn’t the only country eager to get its hand on this vaccine.</p>
<p>Skyrocketing demand coupled with shortages of vital components is leading to bottlenecks in the supply chain of this and other mRNA vaccines, delaying vaccine supplies.</p>
<p>The Victorian government also <a href="https://www.premier.vic.gov.au/victoria-ready-lead-new-vaccine-manufacturing">announced last week</a> it would provide A$50 million to set up local manufacturing of mRNA vaccines in Australia. It’s feasible supply chain issues could also impact local manufacturing of mRNA vaccines.</p>
<p>So what are the missing supplies for making mRNA vaccines?</p>
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Read more:
<a href="https://theconversation.com/what-is-mrna-the-messenger-molecule-thats-been-in-every-living-cell-for-billions-of-years-is-the-key-ingredient-in-some-covid-19-vaccines-158511">What is mRNA? The messenger molecule that's been in every living cell for billions of years is the key ingredient in some COVID-19 vaccines</a>
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<h2>The shortages slowing mRNA vaccine production</h2>
<p><strong>1. mRNA manufacturing and capping</strong></p>
<p>Manufacturing mRNA vaccines is kind of like making a car, with an assembly line and many steps. Each step needs to lead to the next and flow smoothly to make the final product. </p>
<p>COVID mRNA vaccine manufacturing starts with making the “messenger RNA”, the instructions that tell our cells to make the coronavirus’ spike proteins. The mRNA is produced in reactor vessels, where protein enzymes track along a DNA template and copy that DNA sequence into RNA form.</p>
<p>The first shortage is in sterile, single-use plastic bags which sit inside the metal reactor vessels used for making the mRNA, almost like a bin liner. Several suppliers of these plastic liners are <a href="https://www.ft.com/content/b2f4f9cf-af80-428f-a198-2698ceb4c701">ramping up production</a> so it’s anticipated this shortage won’t last too long.</p>
<p>The second main shortage relates to “capping” the mRNA at one end. Capping involves adding a chemical molecule to the mRNA which stops the mRNA breaking down too quickly and helps our cells use the mRNA to make protein. Early on during the worldwide upscaling of mRNA manufacturing, rumours abounded that the enzymes and raw materials to make the mRNA cap were running short, given related enzymes used for COVID tests were also in <a href="https://cen.acs.org/analytical-chemistry/diagnostics/Shortage-RNA-extraction-kits-hampers/98/web/2020/03">short supply</a>. </p>
<p>However, while only a few players <a href="https://uk.finance.yahoo.com/news/nucleotides-market-growth-trends-covid-110900508.html?guccounter=1&guce_referrer=aHR0cHM6Ly93d3cuZ29vZ2xlLmNvbS5hdS8&guce_referrer_sig=AQAAAHT9TQqVB65s3GM9IfZB93re88kb9pAnF6V9n4h1Rhk94u1Z0MM8FHyv_Hao6EidhHEhNe-99VRZtPIQ3t740xsXDzkmY4xGJTFOzUAAmORJi9iEdE9bZPu_2Bl-_DYImw1mPOlwiUfv6njekNtkUa0EQ-puKgT5pcmwx7sUgtbM">dominate the field</a>, this doesn’t seem to be a bottleneck now. But it does still remain one of the most costly parts of the mRNA <a href="https://bioprocessintl.com/sponsored-content/ask-the-expert-high-yield-mrna-production-from-plasmid-to-highly-purified-product/">production process</a>.</p>
<p><strong>2. Lipids in nanoparticles</strong></p>
<p>The main bottleneck right now is the supply of some of the lipids making the nanoparticles that protect the mRNA and deliver it into our cells.</p>
<p>One lipid in particular, a so-called “cationic lipid”, wraps around the mRNA and then releases it inside the cell. Several chemical synthesis steps are required to make these cationic lipids, and prior to COVID only a handful of manufacturers worldwide were making these, and only on a <a href="https://www.washingtonpost.com/business/2021/02/18/vaccine-fat-lipids-supply/">fairly small scale</a>. </p>
<p>Upscaling this production of cationic lipids has been even harder than setting up the mRNA production. Currently, four companies — Croda/Avanti, CordenPharma, Evonik and Merck — are the <a href="https://cen.acs.org/business/outsourcing/Lipids-unsung-COVID-19-vaccine/99/web/2021/02">main manufacturers</a> of these lipids.</p>
<p>As an indication of how serious this shortfall in lipids is, in December 2020 former US President Donald Trump invoked the Defense Production Act to <a href="https://www.ft.com/content/3c21ae81-3504-4d11-8784-c1b67458a0ca">assist Pfizer in accessing</a> more lipids. </p>
<h2>Why do we have these shortages?</h2>
<p>The reasons for these shortages are complex. In most cases, demand has outstripped supply. In some cases, some countries or companies have been stockpiling some of these components. “Operation Warp Speed”, initiated by the Trump administration to speed up COVID vaccine development, used its financial clout <a href="https://www.medicalcountermeasures.gov/barda/influenza-and-emerging-infectious-diseases/coronavirus/pharmaceutical-manufacturing-in-america/">throughout 2020</a> to buy up and secure many vaccine components including vials and lipids. This has put the vaccine manufacturers based in the United States in a good position, including Moderna and several Pfizer sites.</p>
<p>For some materials, the reason for the shortfall is simply that they’re hard to make. The bespoke cationic lipids are chemically synthesised in ten steps that all have to performed under strict quality control. Even if the equipment is ready, setting up such a manufacturing process <a href="https://cen.acs.org/business/outsourcing/Lipids-unsung-COVID-19-vaccine/99/web/2021/02">takes months</a>.</p>
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<h2>How could these shortages impact future mRNA manufacturing in Australia?</h2>
<p>When Victoria’s <a href="https://www.abc.net.au/news/2021-04-21/victoria-to-develop-mrna-covid19-vaccine-facilities/100083372">new mRNA manufacturing facility</a> comes online, hopefully in the next 12-24 months, some of these global shortages may still be plaguing the worldwide supply chains. This shouldn’t stop our efforts on that front as raw material supplies are rapidly increasing. </p>
<p>Australia should also do more manufacturing of small molecule active pharmaceutical ingredients, that is, the <a href="https://www.who.int/medicines/areas/quality_safety/quality_assurance/DefinitionAPI-QAS11-426Rev1-08082011.pdf">biologically active component in each drug</a>, including lipids and other building blocks of mRNA. Australia imports over 90% of its <a href="https://www.afr.com/politics/federal/australia-dangerously-dependent-on-medical-imports-20200217-p541ej">drugs from overseas</a>. Making active pharmaceutical ingredients is important, not just for COVID vaccines but more generally.</p>
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<p>Australia nearly ran out of some essential drugs, <a href="https://thenewdaily.com.au/news/2020/05/02/coronavirus-shortage-medications/">like ventolin</a>, in the early days of the COVID-19 crisis. This was due to both Australians’ panic buying, as well as COVID-hit Chinese factories slowing down their manufacturing, leading to a lack of access to these ingredients for our most <a href="https://thenewdaily.com.au/news/2020/05/02/coronavirus-shortage-medications/">commonly used drugs</a>. The added benefits of locally based manufacturing of active pharmaceutical ingredients is we’d be part of the solution when components are in short supply in future. </p>
<p>Australia also has a very strong research community in mRNA and nanomedicine. There are several world-leading groups working on creating better lipid nanoparticles for the delivery of mRNA and other medical products.</p>
<p>Having access to local manufacturing capability of active pharmaceutical ingredients would therefore transform the ability of Australian researchers to lead the way in developing the next blockbuster medical technology based on mRNA or nanoparticle delivery.</p>
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Read more:
<a href="https://theconversation.com/3-mrna-vaccines-researchers-are-working-on-that-arent-covid-157858">3 mRNA vaccines researchers are working on (that aren't COVID)</a>
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<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 the President of the RNA Network of Australia and a Director of the International RNA Society.</span></em></p><p class="fine-print"><em><span>Pall Thordarson receives funding from the Australian Research Council (ARC), The University of New South Wales, Australian Research Data Commons (ARDC - NCRIS), NSW Health, Cancer Australia and the Kids Cancer project, and the Cooperative Research Centres Projects (CRC-P) scheme with backing from industry partners Genesys Electronic Design and CSL. Pall has been asked to give advise to several organisation and companies that are interest in RNA manufacturing in Australia.</span></em></p>Skyrocketing demand coupled with shortages of vital components is leading to bottlenecks in the supply chain of Pfizer’s and other mRNA vaccines.Archa Fox, Associate Professor and ARC Future Fellow, The University of Western AustraliaPall Thordarson, Professor, Chemistry, UNSW SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1595852021-04-23T12:30:38Z2021-04-23T12:30:38ZNew malaria vaccine proves highly effective – and COVID shows how quickly it could be deployed<p>Coronavirus vaccines have been developed and deployed in record time, but as global rollout has progressed, too few doses have been made available in low-income countries. It’s a stark reminder that when it comes to infectious diseases, the world’s poorest often get left behind.</p>
<p>This is a problem that extends far beyond COVID-19. In Africa, for example, <a href="https://www.statista.com/statistics/1170530/coronavirus-deaths-in-africa/">malaria</a> has probably caused four times as many deaths as <a href="https://www.who.int/news-room/fact-sheets/detail/malaria">COVID-19</a> over the past year. Thankfully, our <a href="https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3830681">new research</a> shows that an effective vaccine against malaria could now be closer than ever before.</p>
<p>For the first time, a vaccine has shown high efficacy in trials – preventing the disease 77% of the time among those receiving it. This is a landmark achievement. The WHO’s target efficacy for malaria vaccines is over 75%. Until now, this level has never been reached.</p>
<p>The speed and success of developing COVID-19 vaccines shows what’s possible, and should be an inspiration to get this malaria vaccine finished, licensed and distributed. It’s important not just because of the threat malaria poses, but also because investing in vaccines can help prepare us for the next pandemic. Work on this vaccine helped speed the development of the Oxford vaccine for COVID-19 as well.</p>
<p>The World Health Organization <a href="https://www.who.int/news-room/fact-sheets/detail/malaria">estimates</a> there were 229 million cases of malaria in 2019. Globally, malaria’s annual death toll stands at over 400,000, with no improvement in the last five years. Two-thirds of this terrible loss is among African children under five years of age.</p>
<p>Billions of dollars are being spent each year on bed nets, insecticide spraying and antimalarial drugs just to keep death rate as it is. New technologies are needed, especially as the WHO is targeting a <a href="https://www.who.int/malaria/areas/global_targets/en/">90% reduction</a> in deaths by 2030.</p>
<p>No malaria vaccine has yet been authorised for use, though the idea of controlling malaria by vaccination has been around for a long time. The first scientific report was from Algiers in 1910. Clinical trials <a href="https://pubmed.ncbi.nlm.nih.gov/20985795/">began in the 1940s</a>, got serious from the 1980s onwards and, today, over 140 malaria vaccine candidates have been tested in humans.</p>
<p>But none has progressed to approval and deployment. The science is tough. The malaria parasite is complex, with more than 5,000 genes, meaning it has many different characteristics for vaccine designers to choose to target. SARS-CoV-2, the virus that causes COVID-19, has just 12 genes, and its <a href="https://theconversation.com/new-coronavirus-variant-what-is-the-spike-protein-and-why-are-mutations-on-it-important-152463">spike protein</a> was the obvious target for vaccine scientists.</p>
<p>Malaria parasites have evolved with humans and their ancestors over the last <a href="https://pubmed.ncbi.nlm.nih.gov/21118608/">30 million years</a>, not only generating a multitude of strains but also impacting our own evolution, with <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733195/">gene variants</a> that lessened the effects of malaria being passed on over time. Worse still, these parasites generate chronic infections in millions, suppressing the human immune response that a vaccine tries to generate.</p>
<h2>New success with a new vaccine</h2>
<p>But progress on malaria vaccine development is accelerating, as illustrated by a new report from a <a href="https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3830681">multi-national group of researchers</a>, including myself, published in the Lancet. The team of <a href="https://www.wwarn.org/about-us/governance-people/professor-halidou-tinto">Professor Halidou Tinto</a>, based in Ouagadougou, Burkina Faso, studied the new R21 malaria vaccine in 450 children – the key population where a vaccine is most urgently needed. They found it to be safe and have unprecedented efficacy in those aged 5-17 months.</p>
<p>In this controlled trial, 105 of the 147 children who received a placebo contracted malaria. But of the 292 who received a dose of the vaccine, only 81 contracted the disease – surpassing the WHO’s 75% target for protection. A phase 3 trial – to test the safety and efficacy of the vaccine in a much larger number of people – will start in four African countries in late April 2021, aiming for accelerated approvals if successful.</p>
<p>Scientists in four continents contributed to the design and testing of this promising vaccine. Design and early development took place at the Jenner Institute at the University of Oxford, where malaria vaccine clinical trials have been pursued since 1999. <a href="https://www.cochranelibrary.com/es/central/doi/10.1002/central/CN-01462017/full">“Challenge” studies</a> in Oxford, Southampton and London, where volunteers are deliberately infected with malaria by mosquito bites to test vaccine efficacy, highlighted the potential of the R21 vaccine. An adjuvant component for the vaccine is required and provided by Novavax, a biotechnology company in the US and Sweden. </p>
<p>Manufacturing of the vaccine is ongoing at the world’s largest vaccine supplier, the Serum Institute of India. This malaria partnership with was already in place last year when COVID-19 struck, allowing us to pivot rapidly to manufacturing the Oxford coronavirus vaccine. (The method it uses for delivery, a chimpanzee adenovirus called ChAdOx1, is a technology previously tested for use against malaria.) Having this collaboration already in place, even prior to our partnership with AstraZeneca, helped the Indian company accelerate its COVID-19 vaccine manufacturing such that today it is producing more doses than anywhere else.</p>
<p>Could the same rapid, large-scale production happen for malaria vaccines? Maybe, but there are risks. Another promising vaccine candidate – from GlaxoSmithKline, called RTS,S – hit <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30815-1/fulltext">safety</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4850267/">issues</a> in its major phase 3 trial five years ago, and this has delayed its approval while further large-scale assessments take place. </p>
<p>Financing will also be required for malaria vaccine deployment, but with the low-cost large-scale manufacturing capacity in India available, an inexpensive widely accessible vaccine should be achievable. However, as COVID-19 is increasing in several parts of Africa, this could potentially impact the R21 vaccine phase 3 trials that are starting soon in Mali, Burkina Faso, Tanzania and Kenya.</p>
<p>The UK has long been a force in global health research, and fighting malaria is a flagship activity. Funding has been hit hard by <a href="https://www.ifs.org.uk/publications/15392">this year’s reduction</a> in the overseas aid budget. But COVID-19 has highlighted the importance of maintaining capacity in vaccine research and development, as well as the feasibility of moving more quickly than ever before to vaccine approval and supply. </p>
<p>One lasting benefit of a terrible pandemic might be a quicker route to a malaria vaccine and a safer future for children in some of the world’s poorest countries.</p><img src="https://counter.theconversation.com/content/159585/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Adrian Hill receives funding from government and charitable funders of malaria vaccine development. He may benefit for a share of any royalty stream to Oxford University from the R21/MM vaccine.</span></em></p>The R21 vaccine protected three-quarters of children against malaria in trials.Adrian Hill, Director of the Jenner Institute, University of OxfordLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1578582021-04-14T20:08:45Z2021-04-14T20:08:45Z3 mRNA vaccines researchers are working on (that aren’t COVID)<figure><img src="https://images.theconversation.com/files/393919/original/file-20210408-21-8z0f13.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1000%2C561&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/messenger-rna-mrna-strand-3d-rendering-1907619631">from www.shutterstock.com</a></span></figcaption></figure><p>The world’s first <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/mrna.html">mRNA vaccines</a> — the COVID-19 vaccines from Pfizer/BioNTech and Moderna — have made it in record time from the laboratory, through successful clinical trials, regulatory approval and into people’s arms.</p>
<p>The high <a href="https://theconversation.com/how-effective-is-the-first-shot-of-the-pfizer-or-moderna-vaccine-156615">efficiency</a> of protection against severe disease, the <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">safety</a> seen in clinical trials and the <a href="https://theconversation.com/less-than-a-year-to-develop-a-covid-vaccine-heres-why-you-shouldnt-be-alarmed-150414">speed</a> with which the vaccines were designed are <a href="https://www.nature.com/articles/nrd.2017.243">set to transform</a> how we develop vaccines in the future. </p>
<p>Once researchers have set up the mRNA manufacturing technology, they can potentially produce mRNA against any target. Manufacturing mRNA vaccines also does not need living cells, making them easier to produce than some other vaccines.</p>
<p>So mRNA vaccines could potentially be used to prevent a range of diseases, not just COVID-19.</p>
<h2>Remind me again, what’s mRNA?</h2>
<p><a href="https://theconversation.com/explainer-what-is-rna-15169">Messenger ribonucleic acid (or mRNA for short)</a> is a type of genetic material that tells your body how to make proteins. The two mRNA vaccines for SARS-CoV-2, the coronavirus that causes COVID-19, deliver fragments of this mRNA into your cells.</p>
<p>Once inside, your body uses instructions in the mRNA to make SARS-CoV-2 spike proteins. So when you encounter the virus’ spike proteins again, your body’s immune system will already have a head start in how to handle it.</p>
<p>So after COVID-19, which mRNA vaccines are researchers working on next? Here are three worth knowing about.</p>
<h2>1. Flu vaccine</h2>
<p>Currently, we need to formulate new versions of the flu vaccine each year to protect us from the <a href="https://theconversation.com/high-dose-immune-boosting-or-four-strain-a-guide-to-flu-vaccines-for-over-65s-112224">strains the World Health Organization (WHO) predicts</a> will be circulating in flu season. This is a constant race to monitor how the virus evolves and how it spreads in real time. </p>
<p>Moderna is already turning its attention to an <a href="https://investors.modernatx.com/news-releases/news-release-details/moderna-provides-business-update-and-announces-three-new">mRNA vaccine against seasonal influenza</a>. This would target the four seasonal strains of the virus the WHO predicts will be circulating.</p>
<p>But the holy grail is a <a href="https://asm.org/Articles/2019/August/A-Universal-Influenza-Vaccine-How-Close-Are-We">universal flu vaccine</a>. This would protect against all strains of the virus (not just <a href="https://theconversation.com/the-2019-flu-shot-isnt-perfect-but-its-still-our-best-defence-against-influenza-120088">what the WHO predicts</a>) and so wouldn’t need to be updated each year. The same researchers who pioneered mRNA vaccines are also <a href="https://www.sciencedirect.com/science/article/pii/S1525001620301994">working on a universal flu vaccine</a>.</p>
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<p>The researchers used the vast amounts of data on the influenza genome to find the mRNA code for the most “highly conserved” structures of the virus. This is the mRNA least likely to mutate and lead to structural or functional changes in viral proteins. </p>
<p>They then prepared a mixture of mRNAs to express four different viral proteins. These included one on the stalk-like structure on the outside of the flu virus, two on the surface, and one hidden inside the virus particle. </p>
<p>Studies in mice show this experimental vaccine is <a href="https://www.sciencedirect.com/science/article/pii/S1525001620301994">remarkably potent</a> against diverse and difficult-to-target strains of influenza. This is a <a href="https://www.abc.net.au/news/health/2021-02-09/covid-19-vaccines-australia-mrna-medical-revolution/13132252">strong contender</a> as a universal <a href="https://www.pennmedicine.org/coronavirus/vaccine/qa-with-drew-weissman">flu vaccine</a>.</p>
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<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>
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<h2>2. Malaria vaccine</h2>
<p><a href="https://www.who.int/news-room/fact-sheets/detail/malaria">Malaria</a> arises through infection with the single-celled parasite <em>Plasmodium falciparum</em>, delivered when mosquitoes bite. There is no vaccine for it.</p>
<p>However, US researchers working with pharmaceutical company GSK have <a href="http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=/netahtml/PTO/srchnum.html&r=1&f=G&l=50&s1=20210030859.PGNR.&OS=DN/20210030859&RS=DN/20210030859">filed a patent</a> for an mRNA vaccine against malaria. </p>
<p>The mRNA in the vaccine codes for a <a href="https://www.nature.com/articles/s41467-018-05041-7">parasite protein</a> called PMIF. By teaching our bodies to target this protein, the aim is to train the immune system to eradicate the parasite.</p>
<p>There have been promising results of the experimental vaccine <a href="https://www.nature.com/articles/s41467-018-05041-7">in mice</a> and early-stage human trials are <a href="https://www.vox.com/future-perfect/22307700/malaria-rna-vaccines-covid-19">being planned</a> in the UK.</p>
<p>This malaria mRNA vaccine is an example of a <a href="https://www.nature.com/articles/s41434-020-00204-y">self-amplifying mRNA vaccine</a>. This means very small amounts of mRNA need to be made, packaged and delivered, as the mRNA will make more copies of itself once inside our cells. This is the next generation of mRNA vaccines after the “standard” mRNA vaccines seen so far against COVID-19.</p>
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<a href="https://theconversation.com/covid-19-isnt-the-only-infectious-disease-scientists-are-trying-to-find-a-vaccine-for-here-are-3-others-145271">COVID-19 isn't the only infectious disease scientists are trying to find a vaccine for. Here are 3 others</a>
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<h2>3. Cancer vaccines</h2>
<p>We already have vaccines that prevent infection with viruses that cause cancer. For example, <a href="https://theconversation.com/we-have-a-vaccine-for-hepatitis-b-but-heres-why-we-still-need-a-cure-122861">hepatitis B vaccine</a> prevents some types of liver cancer and the <a href="https://www.health.gov.au/health-topics/immunisation/immunisation-services/human-papillomavirus-hpv-immunisation-service">human papillomavirus (HPV) vaccine</a> prevents cervical cancer. </p>
<p>But the flexibility of mRNA vaccines lets us think more broadly about tackling cancers not caused by viruses. </p>
<p>Some types of tumours have antigens or proteins not found in normal cells. If we could train our immune systems to identify these tumour-associated antigens then our immune cells could kill the cancer. </p>
<p>Cancer vaccines can be targeted to specific combinations of these antigens. BioNTech is developing one such mRNA vaccine that <a href="https://pubmed.ncbi.nlm.nih.gov/27281205/">shows promise</a> for people with advanced melanoma. CureVac has developed one for a specific type of lung cancer, with results from <a href="https://pubmed.ncbi.nlm.nih.gov/30736848/">early clinical trials</a>.</p>
<p>Then there’s the promise of personalised anti-cancer mRNA vaccines. If we could design an individualised vaccine specific to each patient’s tumour then we could train their immune system to fight their own individual cancer. Several research groups and companies <a href="https://www.youtube.com/watch?v=zM97kg7atWw">are working on this</a>.</p>
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<h2>Yes, there are challenges ahead</h2>
<p>However, there are several hurdles to overcome before mRNA vaccines against other medical conditions are used more widely.</p>
<p>Current mRNA vaccines need to be <a href="https://www.abc.net.au/news/health/2021-04-12/pfizer-temperature-changes-transport-fridge-freezer/100062594">kept frozen</a>, limiting their use in developing countries or in remote areas. But Moderna is working on developing an mRNA vaccine that can be <a href="https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-longer-shelf-life-its-covid-19-vaccine#:%7E:text=The%20ability%20to%20store%20our,other%20parts%20of%20the%20world.%E2%80%9D">kept in a fridge</a>.</p>
<p>Researchers also need to look at how these vaccines are delivered into the body. While injecting into the muscle works for mRNA COVID-19 vaccines, delivery into a vein may be better for cancer vaccines. </p>
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<a href="https://theconversation.com/4-things-about-mrna-covid-vaccines-researchers-still-want-to-find-out-154160">4 things about mRNA COVID vaccines researchers still want to find out</a>
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<p>The vaccines need to be shown to be safe and effective in large-scale human clinical trials, ahead of regulatory approval. However, as regulatory bodies around the world have already approved mRNA COVID-19 vaccines, there are far fewer regulatory hurdles than a year ago. </p>
<p>The high cost of personalised mRNA cancer vaccines may also be an issue.</p>
<p>Finally, not all countries have the facilities to make mRNA vaccines on a large scale, <a href="https://theconversation.com/australia-may-miss-out-on-several-covid-vaccines-if-it-cant-make-mrna-ones-locally-148996">including Australia</a>.</p>
<p>Regardless of these hurdles, mRNA vaccine technology has been described as <a href="https://www.tandfonline.com/doi/full/10.4161/hv.25181">disruptive</a> and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3991152/">revolutionary</a>. If we can overcome these challenges, we can potentially change how we make vaccines now and into the future.</p><img src="https://counter.theconversation.com/content/157858/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. She is President of the RNA Network of Australia and an elected Director of the International RNA Society </span></em></p><p class="fine-print"><em><span>Damian Purcell receives funding from the National Health and Medical Research Council, and the Jack Ma Foundation. He is Past Presidents' advisor for the Australasian Virology Society, and Treasurer of the RNA Network of Australia,</span></em></p>We have two mRNA COVID-19 vaccines so far. But what else can this technology do?Archa Fox, Associate Professor and ARC Future Fellow, The University of Western AustraliaDamian Purcell, Professor of virology and theme leader for viral infectious diseases, The Peter Doherty Institute for Infection and ImmunityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1581642021-03-31T15:35:45Z2021-03-31T15:35:45ZCOVID-19 vaccines are a victory for public research, not ‘greed’ and ‘capitalism’<p>Boris Johnson, the UK prime minister, reportedly <a href="https://www.bbc.com/news/uk-politics-56504546">attributed the success of the COVID-19</a> vaccines to “capitalism” and “greed”. But he is wrong – the idea that private ingenuity and naked competition produced the vaccines is a complete fantasy.</p>
<p>Before COVID-19, the vaccine market was notoriously sluggish, taking between <a href="https://coronavirus.jhu.edu/vaccines/timeline">five</a> and <a href="https://www.ifpma.org/wp-content/uploads/2019/07/IFPMA-ComplexJourney-2019_FINAL.pdf">15 years</a> to develop a viable candidate. It is for this reason the current effort looks so remarkable.</p>
<p>For pharmaceutical companies, the incentives are poor. In April 2018, long before coronavirus emerged, a report by <a href="https://www.cnbc.com/2018/04/11/goldman-asks-is-curing-patients-a-sustainable-business-model.html">Goldman Sachs analysts proposed</a> that providing a “one shot” cure for diseases could never be a “sustainable business model”. </p>
<p>That’s because, as Johnson rightly implies, pharmaceutical companies follow the money. In 2019, the <a href="http://www.globenewswire.com/news-release/2020/07/16/2063440/0/en/Vaccines-Market-to-Reach-USD-104-87-Billion-by-2027-Introduction-of-World-s-First-Malaria-Vaccine-in-Malawi-to-Lighten-Business-Possibilities-states-Fortune-Business-Insights.html">global vaccines market size</a> was US$47bn. Meanwhile sales of just <a href="https://www.pharmamanufacturing.com/articles/2020/pharmas-biggest-blockbusters">four treatment drugs</a> matched this volume of sales (Humira, used to treat rheumatoid arthritis; Keytruda, the cancer treatment; Revlimid, used to treat multiple myeloma; and Imbruvica, also a cancer drug). </p>
<p>Earlier coronavirus diseases, Sars and Mers, <a href="https://jbiomedsci.biomedcentral.com/articles/10.1186/s12929-020-00695-2">had no vaccine</a>. Both had candidates <a href="https://theconversation.com/the-mysterious-disappearance-of-the-first-sars-virus-and-why-we-need-a-vaccine-for-the-current-one-but-didnt-for-the-other-137583">initially tested on animals</a> that did not make it to <a href="https://www.who.int/blueprint/priority-diseases/key-action/list-of-candidate-vaccines-developed-against-mers.pdf">human trials</a>. The Ebola vaccine was <a href="https://www.nature.com/articles/d41586-019-03490-8">finally approved</a> in 2019, 16 years after it was first patented and a full six years after the start of the epidemic in West Africa. </p>
<p>There can be little doubt that <a href="https://harvardlawreview.org/2013/06/racial-capitalism/">racial capitalism</a> and global economics has shaped our response to this virus. Previous viruses did not threaten the economy of the developed countries to the same extent. The <a href="https://www.reuters.com/article/us-health-ebola-cost-idUSKCN1MY2F8">costs of Ebola to west African countries is estimated at more than US$50b</a>. The cost of Sars was significant for the Asian economy, amounting to <a href="https://www.bbc.co.uk/blogs/thereporters/stephanieflanders/2009/04/economic_impact_of_swine_flu.html">between 0.5 and 2.0% of GDP</a>. The economic fallout of Mers was <a href="https://www2.deloitte.com/content/dam/insights/us/articles/63584_Economic-effects-of-past-epidemics/DI_Economic-effects-of-past-epidemics.pdf">largely limited to the South Korean economy</a>. </p>
<p>Most advanced economies stand to lose <a href="https://www.statista.com/topics/6139/covid-19-impact-on-the-global-economy">at least 4.5% of GDP</a> as a result of this pandemic. So we needed COVID-19 vaccines to save these economies. Does that count as a success for greed and capitalism?</p>
<h2>A victory for public funds</h2>
<p>The reason the COVID-19 vaccines arrived at such warp speed is that <a href="https://corporatewatch.org/five-ways-big-pharma-makes-so-much-money/">the risk model</a> changed overnight and the normal risks associated with vaccine development were almost completely removed from investors. Before this pandemic, capitalism was not very good at delivering vaccines for infectious diseases. </p>
<p>Research and development, combined with direct subsidies were mobilised on an enormous scale for this pandemic. Governments used public funds to place huge advance orders for vaccines that removed all market risk from future sales. </p>
<p>It is those two things that prompted an unprecedented single-purpose investment in the sector. This investment will, of course, be followed by <a href="https://corporatewatch.org/vaccine-capitalism-a-run-down-of-the-huge-profits-being-made-from-covid-19-vaccines/">unprecedented profits</a>.</p>
<p>The development of the COVID-19 vaccines is, therefore, part of a vast system of public subsidy that can deceive people into thinking that it is private capital that is saving us from the virus, thanks to its capacity for “innovation”. </p>
<p>Yet there is another subsidy to those companies that remains hidden – universities.</p>
<p>Universities provide trained scientists and a foundation of knowledge that emerges over hundreds of years. It is in universities that the rules for clinical research are developed, and it is university researchers who publish results in academic journals which provide that knowledge foundation. </p>
<p>Universities make the largest social contribution to verifying and disseminating scientific breakthroughs. It is knowledge that we hold in common. In economic terms, this knowledge production counts as an “externality” in the business model: an invisible subsidy that never shows up on a corporate balance sheet, because corporations never have to pay for them.</p>
<p>The infrastructure that produced the COVID-19 vaccines was nurtured in publicly funded universities, in public institutes and in heavily subsidised private labs. A process that looks like it is driven by private ingenuity and naked competition in reality is driven by the scientific knowledge that is part of the “commons” and for this reason should be owned by everyone on the planet.</p><img src="https://counter.theconversation.com/content/158164/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>This is part of a collaborative project with Corporate Watch titled 'Vaccination Capitalism'. Earlier work on the project was funded by Leverhulme Trust Grant MRF-2016-091.</span></em></p>The development of the COVID-19 vaccines is part of a vast system of public subsidies and universities, not corporate ambition.David Whyte, Professor of Socio-legal Studies, University of LiverpoolLicensed 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>
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<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>
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<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>
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<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>
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<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>
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<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>
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<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/1515902021-01-14T22:54:53Z2021-01-14T22:54:53ZTuberculosis kills as many people each year as COVID-19. It’s time we found a better vaccine<p>In July 1921, a French infant became the first person to <a href="https://pubmed.ncbi.nlm.nih.gov/24023600/">receive</a> an experimental vaccine against tuberculosis (TB), after the mother had died from the disease. The vaccine, known as Bacille Calmette-Guérin (BCG), is the same one still used today.</p>
<p>This first dose of BCG was the culmination of 13 years of research and development. </p>
<p>BCG remains the only licensed vaccine against TB and 2021 marks its <a href="https://pubmed.ncbi.nlm.nih.gov/24023600/">100th anniversary</a>. </p>
<p>Today, all eyes are on the rollout of the COVID-19 vaccine. But while the number of people who died from COVID-19 in the last year is shocking, TB kills about the same number of people — about 1.5-2 million — each year, and has done so for many decades.</p>
<p>In fact, it’s estimated that over the last 200 years, more than 1 billion people have died from TB, <a href="https://www.nature.com/articles/502S2a">far more than from any other infectious disease</a>. </p>
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Read more:
<a href="https://theconversation.com/covid-19-isnt-the-only-infectious-disease-scientists-are-trying-to-find-a-vaccine-for-here-are-3-others-145271">COVID-19 isn't the only infectious disease scientists are trying to find a vaccine for. Here are 3 others</a>
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<h2>If we have a vaccine, why do so many people still die from TB?</h2>
<p>Tuberculosis is caused by the bacterium <em>Mycobacterium tuberculosis</em>. It’s transmitted when a person with active TB coughs up aerosol droplets, which are then inhaled by someone else. </p>
<p>There are about <a href="https://www.who.int/health-topics/tuberculosis#tab=tab_1">10 million cases</a> of active TB annually, and it’s <a href="https://www.who.int/teams/global-tuberculosis-programme/tb-reports">estimated</a> up to 2 billion people are what’s known as “latently infected”. That means they are not sick and do not transmit the disease, but in about 10% of these people the disease reactivates. </p>
<p>In most TB endemic regions of the world, BCG is given to infants shortly after birth. The vaccination prevents childhood versions of TB and <a href="https://pubmed.ncbi.nlm.nih.gov/16616560/">saves thousands of children’s lives annually</a>. </p>
<p>However, the efficacy of BCG wanes over time. In other words, it stops working. Protection against TB is often lost by adolescence or early adulthood.</p>
<p>Importantly, BCG doesn’t prevent active lung TB in adults, the most important driver of ongoing transmission and cause of death. </p>
<p>The <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)60570-0/fulltext">World Health Organization has a goal of TB elimination</a>. To do that, we need to find a TB vaccine that also works in adults.</p>
<h2>Why hasn’t BCG been replaced with a more effective TB vaccine?</h2>
<p>Over the last decades only <a href="https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(19)30274-7/fulltext">about 15 new TB vaccine candidates have entered clinical trials</a> (versus <a href="https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines">63 for COVID-19</a> in one year).</p>
<p>Worryingly, many of the most advanced TB vaccine candidates work no better than BCG.</p>
<p>Because the current TB vaccine candidate pipeline is relatively small, these setbacks and trial “failures” mean BCG may remain the gold standard for many years to come. </p>
<p>Despite being 100 years old, exactly how BCG vaccine works is largely unknown. It’s unclear why BCG usually only confers protection against childhood versions of TB or why protection wanes in adolescence.</p>
<p>Given those uncertainties, we can count ourselves lucky the bureaucratic hurdles for vaccine development were significantly lower in the 1920s.</p>
<p>If BCG were developed today, it would probably never be used; the current complex regulatory framework for vaccine development and licensing would likely not allow the use of a vaccine for which nothing or little is known about how it works. </p>
<p>The reasons BCG hasn’t been replaced with a more effective TB vaccine include:</p>
<ul>
<li><p>the decline of TB in many Western countries in the 20th century</p></li>
<li><p>limited interest from pharmaceutical companies to invest in TB vaccine development</p></li>
<li><p>the fact TB research and pre-clinical vaccine development is logistically challenging and requires special biological containment facilities</p></li>
<li><p>the short-term and fiercely competitive environment for government and philanthropic research funding makes it difficult for academics to commit to TB vaccine research as a career path.</p></li>
</ul>
<h2>Where there’s a will, there’s a way</h2>
<p>The pace of COVID-19 vaccine development shows what’s possible when the political will, pharmaceutical interest and funding is there. </p>
<p>While TB is no longer widespread in Australia, it is an issue in remote Indigenous communities. </p>
<p>Papua New Guinea, Australia’s closest neighbour, has high rates of multi-drug resistant TB and low BCG coverage rates. TB has been introduced into Australia via the Torres Strait, with a high proportion of <a href="https://wwwnc.cdc.gov/eid/article/25/3/18-1003_article">cross-border diagnoses</a> in North Queensland and <a href="https://pubmed.ncbi.nlm.nih.gov/28225336/">over-representation of Indigenous children</a>.</p>
<p>Resistance to current TB treatments increases steadily. Treatment of multi drug-resistant TB is hugely expensive and can take up to two years, requiring <a href="https://pubmed.ncbi.nlm.nih.gov/24751166/">multiple antibiotics and close monitoring</a>. </p>
<p>Now is the time to put financial and political will into finding a more effective TB vaccine. </p>
<p>2020 taught us pathogens can cause enormous harm to societies and economies. Investment into infectious disease research and vaccine development represents a fraction of the economic cost of a pandemic. </p>
<p>Tuberculosis is a global threat and a public health concern on a scale similar to COVID-19. The development of a new and effective TB vaccine is crucial if TB is to be significantly reduced, let alone eradicated.</p>
<p>Although the anniversary of BCG is cause for celebration, it should also serve as a reminder more needs to be done to combat this deadly disease. </p>
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Read more:
<a href="https://theconversation.com/just-as-in-coronavirus-young-people-are-key-to-stopping-tuberculosis-133745">Just as in coronavirus, young people are key to stopping tuberculosis</a>
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<img src="https://counter.theconversation.com/content/151590/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Andreas Kupz has received grants and fellowships from the NHMRC and the Far North Queensland Hospital Foundation to work on tuberculosis vaccine development. He is co-Chair of the Live Attenuated Vaccines Research Community and a member of the Advisory Council of the Collaboration for Tuberculosis Vaccine Discovery (CTVD) consortium at the Bill and Melinda Gates Foundation.</span></em></p>Tuberculosis is a global threat and a public health concern on a scale similar to COVID-19.Andreas Kupz, Senior Research Fellow, James Cook UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1531352021-01-13T10:52:15Z2021-01-13T10:52:15ZOxford scientists: how we developed our COVID-19 vaccine in record time<figure><img src="https://images.theconversation.com/files/378294/original/file-20210112-21-1qkrwh.jpg?ixlib=rb-1.1.0&rect=165%2C143%2C7183%2C4759&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">University of Oxford</span></span></figcaption></figure><p>The pandemic is only a year old, but we already have multiple vaccines available to fight COVID-19 – including the vaccine developed by the team we’re part of at the University of Oxford.</p>
<p>With our partner AstraZeneca, we have submitted both interim <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/fulltext">efficacy data</a> and safety data for the vaccine to regulators across the world for independent scrutiny and approval. So far the vaccine has been approved for emergency use in the UK, India, Morocco, Argentina and El Salvador.</p>
<p>As well as being great news for getting us back to normal, this represents a phenomenal scientific achievement. Typically, developing a vaccine takes decades – but we have several available for COVID-19 after just 12 months. Here’s how we managed this for the Oxford vaccine.</p>
<h2>A head-start on development</h2>
<p>Our vaccine works by delivering the genetic sequence of the SARS-CoV-2 spike protein to the body’s cells (the spike proteins are the distinctive structures that “crown” the coronavirus’s surface). The body’s cells read this genetic code and start producing copies of the spike protein, and the immune system then mounts a response against these proteins and remembers them. This means that if SARS-CoV-2 later enters the body, its spike proteins will immediately flag it to the immune system for destruction.</p>
<p>This may sound complicated, but when the pandemic arrived, we had a head start, as we had <a href="https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0040385&type=printable">already developed</a> a delivery method – or “platform” – for our vaccine and had been testing it for other diseases for almost ten years. Known as the ChAdOx1 <a href="https://www.sciencedirect.com/science/article/abs/pii/S0952791516300541?via%3Dihub">viral vector technology</a>, this platform was created by modifying a harmless adenovirus that causes the common cold in chimpanzees.</p>
<p>ChAdOx1 was chosen as it can generate a strong immune response and is not a replicating virus, so cannot cause an infection. It had already been used safely in thousands of subjects in clinical trials of vaccines for <a href="https://www.sciencedirect.com/science/article/pii/S0264410X1931504X?via%3Dihub">other</a> <a href="https://www.cell.com/action/showPdf?pii=S1525-0016%2816%2931190-X">diseases</a> including <a href="http://www.thelancet.com/retrieve/pii/S1473309920301602">Middle Eastern respiratory syndrome</a> (Mers), which is caused by another type of coronavirus.</p>
<p>Our ongoing research into ChAdOx1 was part of preparing for <a href="https://www.who.int/activities/prioritizing-diseases-for-research-and-development-in-emergency-contexts">“Disease X”</a>, one of eight diseases prioritised for research by the World Health Organization (WHO) due to the risk they pose to public health. COVID-19 has since been added to this list.</p>
<p>Disease X is a placeholder name that highlights that the next serious epidemic could be caused by a pathogen as yet unknown to scientists, which is what happened with the coronavirus.</p>
<figure class="align-center ">
<img alt="A woman scientist sat in a lab using a pipette behind a protective screen." src="https://images.theconversation.com/files/378290/original/file-20210112-15-1iy5j2h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/378290/original/file-20210112-15-1iy5j2h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/378290/original/file-20210112-15-1iy5j2h.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/378290/original/file-20210112-15-1iy5j2h.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/378290/original/file-20210112-15-1iy5j2h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/378290/original/file-20210112-15-1iy5j2h.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/378290/original/file-20210112-15-1iy5j2h.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">Having an already developed platform ready meant that testing of the vaccine could begin quickly.</span>
<span class="attribution"><span class="source">University of Oxford</span></span>
</figcaption>
</figure>
<p>Once researchers in China had mapped the genetic sequence of the coronavirus, we were able to quickly produce <a href="https://covid19vaccinetrial.co.uk/about">our COVID-19 vaccine</a> by combining the ChAdOx1 vector with the genetic sequence of the SARS-CoV-2 spike protein.</p>
<p>The preparation for Disease X ultimately allowed our research team to move straight into testing our vaccine in <a href="https://www.nature.com/articles/s41586-020-2608-y">animals</a> in early 2020, and then to combine the data from <a href="https://www.nature.com/articles/s41541-020-00221-3">these tests</a> with data we had already gathered in previous trials using ChAdOx1, to show that what we were developing worked.</p>
<h2>Making human trials more efficient</h2>
<p>With good data from our animal studies, we were ready to move onto clinical trials – essentially a series of tests to show that a treatment is safe and effective in humans.</p>
<p>Vaccine trials are typically split into <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944327/">three phases</a>. Phase 1 assesses the safety of a vaccine and how well it is tolerated, as well as the immune response. Phase 2 involves testing on a larger, more diverse group of people and is used to identify the optimal dose and schedule.</p>
<p>Phase 3 then aims to test the safety and efficacy of a vaccine in a large group of people, often in multiple locations. This is usually assessed by monitoring how many cases of the disease are seen in a group that gets the vaccine versus a group that doesn’t.</p>
<p>Ordinarily, the different trial phases are run separately, often with time between them for preparing protocols and funding applications, then seeking ethical and regulatory approvals. But for our vaccine, we undertook combined phase 1 and 2 and phase 2 and 3 trials to speed up the development process. This doesn’t mean that any of the required steps were missed out, but rather that we could launch the next stage of the trial as soon as we had collected enough data from the previous phase and had it reviewed by the independent Data Safety Monitoring Board.</p>
<h2>Moving quickly but safely</h2>
<p>Some people have questioned the speed of vaccine development during the pandemic. However, the Oxford COVID-19 vaccine trial – which is still ongoing – is undergoing the same intense scrutiny as other vaccine trials.</p>
<figure class="align-center ">
<img alt="A nurse vaccinating a woman in her upper arm" src="https://images.theconversation.com/files/378287/original/file-20210112-13-mwri9e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/378287/original/file-20210112-13-mwri9e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/378287/original/file-20210112-13-mwri9e.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/378287/original/file-20210112-13-mwri9e.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/378287/original/file-20210112-13-mwri9e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/378287/original/file-20210112-13-mwri9e.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/378287/original/file-20210112-13-mwri9e.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">Interim analysis has shown that the vaccine is safe and effective, but the final stages of its phase 3 trial are still being completed.</span>
<span class="attribution"><span class="source">University of Oxford</span></span>
</figcaption>
</figure>
<p>Throughout, all participants are being closely monitored, and a report is made about anyone who has a medically significant illness or is hospitalised, for whatever cause, even a broken leg. If any of these events is thought to be possibly related to the vaccine, an independent review takes place to carefully assess the medical information. While this happens, vaccinations are paused. They’re then restarted once the review is complete and it is considered safe to continue.</p>
<p>All told, the vaccine will have been tested on almost five times as many volunteers as is usually required for licensing a vaccine. By the end of the trials we’re running, 24,000 people will have taken part in four countries and another 30,000 in trials run by our partners. Testing in different populations is crucial, as any vaccine developed for COVID-19 is likely to be deployed to a large number of people worldwide.</p><img src="https://counter.theconversation.com/content/153135/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>What normally takes decades has been achieved in 12 months, without cutting corners.Tonia Thomas, Vaccine Knowledge Project Manager, University of OxfordRachel Colin-Jones, Visiting Academic, Centre for Clinical Vaccinology and Tropical Medicine, University of OxfordLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1520642020-12-18T18:35:35Z2020-12-18T18:35:35ZInternational Statistic of the Year: Race for a COVID-19 vaccine<figure><img src="https://images.theconversation.com/files/375766/original/file-20201217-19-10qrley.jpg?ixlib=rb-1.1.0&rect=41%2C0%2C4235%2C3075&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">On Dec. 8, 2020, the first members of the public were given doses of a coronavirus vaccine.</span> <span class="attribution"><a class="source" href="https://newsroom.ap.org/detail/APTOPIXVirusOutbreakBritain/ddcd12f559fd44c4a77d2c9d29c5aedd/photo?Query=first%20covid%20vaccine%20uk&mediaType=photo&sortBy=&dateRange=Anytime&totalCount=233&currentItemNo=1">AP Photo/Frank Augstein, Pool</a></span></figcaption></figure><figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/375776/original/file-20201217-17-1aldoja.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/375776/original/file-20201217-17-1aldoja.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=255&fit=crop&dpr=1 600w, https://images.theconversation.com/files/375776/original/file-20201217-17-1aldoja.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=255&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/375776/original/file-20201217-17-1aldoja.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=255&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/375776/original/file-20201217-17-1aldoja.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=321&fit=crop&dpr=1 754w, https://images.theconversation.com/files/375776/original/file-20201217-17-1aldoja.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=321&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/375776/original/file-20201217-17-1aldoja.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=321&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="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
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</figure>
<p>Scientists in China published the complete <a href="https://www.cidrap.umn.edu/news-perspective/2020/01/china-releases-genetic-data-new-coronavirus-now-deadly">genetic sequence of SARS-CoV-2</a> on Jan. 10, 2020. On Dec. 8, 2020, health officials in London <a href="https://www.cbsnews.com/news/covid-19-vaccine-pfizer-uk-first-dose-v-day/">began administering</a> an effective coronavirus vaccine to the public. The global scientific community successfully developed a COVID-19 vaccine in just 332 days.</p>
<p><a href="https://scholar.google.com/citations?user=UtiewDkAAAAJ&hl=en&oi=ao">I am a statistician</a>, and this year I was on the judging panel for the Royal Statistical Society’s <a href="https://www.rss.org.uk/policy-campaigns/campaigns/statistics-of-the-year/">International Statistic of the Year</a>. Much like Oxford English Dictionary’s “Word of the Year” competition, we choose one statistic that is meant to capture the zeitgeist of the year. </p>
<p>The statistic 332 days was the clear, standout winner. After a year of terrible tragedy, economic hardship and sorrow, this number represents an unparalleled collaboration in the history of medicine that gives hope for a return to normality in 2021. </p>
<figure class="align-center ">
<img alt="A researcher working with vials of COVID-19 in a lab." src="https://images.theconversation.com/files/375768/original/file-20201217-19-7gjm5q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/375768/original/file-20201217-19-7gjm5q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/375768/original/file-20201217-19-7gjm5q.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/375768/original/file-20201217-19-7gjm5q.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/375768/original/file-20201217-19-7gjm5q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/375768/original/file-20201217-19-7gjm5q.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/375768/original/file-20201217-19-7gjm5q.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">Vaccine development normally takes around 10 years.</span>
<span class="attribution"><a class="source" href="https://newsroom.ap.org/detail/VirusOutbreak/ee2ba13bb7404e7a80feae160668bec9/photo?Query=vaccine%20research%20lab&mediaType=photo&sortBy=&dateRange=Anytime&totalCount=87&currentItemNo=15">AP Photo/Jessica Hill, File</a></span>
</figcaption>
</figure>
<h2>Fastest vaccine development ever</h2>
<p>In 1981, researchers established the link between <a href="https://dx.doi.org/10.2147%2Ftcrm.2006.2.3.259">human papillomavirus and cervical cancer</a>, a disease that still causes <a href="https://doi.org/10.1016/S2214-109X(19)30482-6">hundreds of thousands of deaths per year</a> worldwide. But it wasn’t until 2006, over 25 years later, that the first <a href="https://www.nvic.org/vaccines-and-diseases/HPV/vaccine-history.aspx">HPV vaccine was developed</a> in the U.S. </p>
<p>On average, it <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5518734/">takes over 10 years</a> to develop a vaccine. Prior to this year, the fastest vaccine development was for the mumps vaccine. That <a href="https://www.nationalgeographic.com/science/2020/04/why-coronavirus-vaccine-could-take-way-longer-than-a-year/#close">took four years</a>. </p>
<p>In April 2020, The New York Times played out multiple scenarios with vaccine experts as to how long it would take to get a SARS-CoV-2 vaccine. Under <a href="https://www.nytimes.com/interactive/2020/04/30/opinion/coronavirus-covid-vaccine.html">normal circumstances</a>, experts estimated, a vaccine would be ready by November 2033.</p>
<p>So how is it possible that researchers got a vaccine to market in just 332 days?</p>
<figure class="align-center ">
<img alt="The White House at night." src="https://images.theconversation.com/files/375769/original/file-20201217-15-1bniqlj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/375769/original/file-20201217-15-1bniqlj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/375769/original/file-20201217-15-1bniqlj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/375769/original/file-20201217-15-1bniqlj.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/375769/original/file-20201217-15-1bniqlj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/375769/original/file-20201217-15-1bniqlj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/375769/original/file-20201217-15-1bniqlj.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">Massive government funding played a big role in getting the vaccine done so fast.</span>
<span class="attribution"><a class="source" href="https://newsroom.ap.org/detail/TrumpGovernmentShutdown/016ea37ed7f4429293b7cb02b7f872f0/photo?Query=White%20AND%20house&mediaType=photo&sortBy=&dateRange=Anytime&totalCount=132439&currentItemNo=10">AP Photo/Susan Walsh</a></span>
</figcaption>
</figure>
<h2>Government financial investment</h2>
<p>A number of things helped to get this vaccine done fast, including international collaboration of unseen proportions, an expedited trial phase process and the biology of the virus itself. In addition to these efforts, one very important reason for the incredible speed was the huge amount of investment made by governments at the very beginning of the pandemic. </p>
<p>Usually, pharmaceutical companies have <a href="https://www.nytimes.com/interactive/2020/04/30/opinion/coronavirus-covid-vaccine.html">limited resources</a> they are willing to spend on vaccine development, and usually, governments are <a href="https://www.cfr.org/backgrounder/what-world-doing-create-covid-19-vaccine">not willing</a> to sink endless money into a process that they aren’t sure is going to work.</p>
<p>The COVID-19 pandemic has thrown the entire playbook to the wind. As of writing this, <a href="https://www.bioworld.com/COVID19products">641 therapies and 189 vaccines</a> related to COVID-19 are under development, most of which are government-funded.</p>
<p>The U.S. government invested in multiple vaccines with the understanding that some of them wouldn’t work, but with the hope that a few would. Under <a href="https://www.hhs.gov/coronavirus/explaining-operation-warp-speed/index.html">Operation Warp Speed</a>, the U.S. government quickly pledged almost US$9 billion to fund vaccine development and production. Moderna – whose <a href="https://www.nytimes.com/2020/11/16/health/Covid-moderna-vaccine.html">vaccine is expected to become the second authorized for U.S. use after Pfizer’s,</a> received a little under $1 billion of federal funding, with a further $1.5 billion for 100 million doses. While this number alone is not surprising – vaccines tend to cost between <a href="https://www.washingtonpost.com/news/wonk/wp/2014/11/18/does-it-really-cost-2-6-billion-to-develop-a-new-drug/">$521 million and $2.1 billion to develop</a> – this was just one of many expensive projects. </p>
<p>Funding from governments and private donors also went toward building manufacturing facilities with the assumption that a vaccine was imminent and the usual regulatory hurdles would be passed quickly. For example, the Bill and Melinda Gates Foundation <a href="https://www.businessinsider.com/bill-gates-factories-7-different-vaccines-to-fight-coronavirus-2020-4">helped fund seven factories</a> back in April, even though only one or two of the factories will actually be used.</p>
<p>This influx of money into multiple vaccines and early preparation for manufacturing was instrumental toward getting a vaccine developed and distributed in record time. The development of COVID-19 vaccines is a testament to the ingenuity, dedication and collaborative efforts of the scientific community. At the end of a seemingly hopeless year, there is a light at the end of the tunnel.</p>
<p>[<em>Get facts about the coronavirus and the latest research.</em> <a href="https://theconversation.com/us/newsletters/the-daily-3?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=coronavirus-facts">Sign up for The Conversation’s newsletter.</a>]</p><img src="https://counter.theconversation.com/content/152064/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Liberty Vittert is an Ambassador for the Royal Statistical Society and a Judge for the Royal Statistical Society's Statistic of the Year.</span></em></p>The coronavirus vaccine was developed faster than any vaccine in history. It took just 332 days from the first sequencing of the virus genome to the first vaccines given to the public.Liberty Vittert, Professor of the Practice of Data Science, Washington University in St. LouisLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1517392020-12-14T14:54:53Z2020-12-14T14:54:53ZCan a pharma company change? Profit, not altruism, motivates COVID-19 vaccine development<figure><img src="https://images.theconversation.com/files/374158/original/file-20201210-13-1dbvyqi.jpg?ixlib=rb-1.1.0&rect=0%2C53%2C5910%2C3934&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The pharmaceutical industry opposes the suspension of intellectual property rights on COVID-19 vaccines and treatments, and no pharma companies have yet contributed to the COVID-19 Technology Access Pool.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>Health Canada <a href="https://www.cbc.ca/news/politics/vaccine-rollout-plan-phac-1.5833912">announced its approval of Pfizer’s COVID-19 vaccine</a> on Dec. 9. Earlier, the news that the same <a href="https://doi.org/10.1038/d41586-020-03441-8">vaccine was on the way</a> in the United Kingdom — and that others are not far behind — was a relief to people all over the world, or at least those in <a href="https://theconversation.com/as-u-s-buys-up-remdesivir-vaccine-nationalism-threatens-access-to-covid-19-treatments-141952">developed countries that can afford the vaccine</a>. </p>
<p>The arrival of the vaccine also seems to have boosted public approval for the pharmaceutical industry. Globally, the industry’s “<a href="https://www.theguardian.com/business/2020/dec/04/covid-vaccines-offer-chance-for-big-pharma-to-improve-its-image">trust and like score</a>” grew to over 68 per cent of people surveyed in 2020 from 65 per cent in 2018.</p>
<p>The bump in the industry’s score was probably helped by the September joint pledge from nine companies that they would “<a href="https://www.nytimes.com/2020/09/08/health/9-drug-companies-pledge-coronavirus-vaccine.html">stand with science</a>” and not try to get a vaccine approved until it had been thoroughly tested for efficacy and safety. This statement was widely seen as the companies standing up to U.S. President Donald Trump, who was making promises about an “<a href="https://www.nbcnews.com/health/health-news/signs-october-vaccine-surprise-alarm-scientists-n1240617">October surprise</a>” in a bid to enhance his re-election chances.</p>
<p>Can a drug company change? The evidence is not clear cut. </p>
<p>The AstraZeneca vaccine is a case in point. The company has promised not to make a profit from the vaccine during the pandemic and is going to sell it at <a href="https://www.cnbc.com/2020/11/17/covid-vaccines-how-much-they-cost-whos-bought-them-and-how-theyre-stored.html">US$3 to US$4 per dose</a>, a price that is one-fifth to one-tenth the cost of the other leading vaccine contenders from Pfizer, Moderna and Johnson & Johnson. </p>
<figure class="align-right ">
<img alt="External view of AstraZeneca building" src="https://images.theconversation.com/files/373784/original/file-20201209-21-1jwntsl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/373784/original/file-20201209-21-1jwntsl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/373784/original/file-20201209-21-1jwntsl.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/373784/original/file-20201209-21-1jwntsl.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/373784/original/file-20201209-21-1jwntsl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/373784/original/file-20201209-21-1jwntsl.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/373784/original/file-20201209-21-1jwntsl.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">AstraZeneca, whose Cambridge, U.K. offices are seen here in July 2020, has pledged not to profit from its COVID-19 vaccine during the pandemic, but also reserved the right to declare when the pandemic is over.</span>
<span class="attribution"><span class="source">(AP Photo/Alastair Grant)</span></span>
</figcaption>
</figure>
<p>The company is also making deals with <a href="https://www.gavi.org">Gavi, the Vaccine Alliance,</a> and has a licensing agreement with Serum Institute of India to <a href="https://apnews.com/article/virus-outbreak-europe-medication-a1ec6915874850dfd38b062f08d04629">supply low- and middle-income countries</a>. According to the company’s CEO Pascal Soriot, “We want to cover the whole world so everyone can get access to this vaccine.” </p>
<p>At the same time, when there was a possible safety problem in September and AstraZeneca’s clinical trials had to be temporarily stopped, the company <a href="https://www.statnews.com/2020/09/09/astrazeneca-covid19-vaccine-pascal-soriot-transparency/">disclosed the information on a conference call with JP Morgan clients</a>, but didn’t make the same information public. </p>
<p>AstraZeneca has also reserved the right to declare when the pandemic is over, which could be as early as July 2021 according to a <a href="https://www.ft.com/content/c474f9e1-8807-4e57-9c79-6f4af145b686">document seen by the <em>Financial Times</em></a>. Presumably at that time the price will go up, although Soriot has not disclosed what that price will be.</p>
<h2>Intellectual property</h2>
<p><a href="https://doi.org/10.1016/S0140-6736(20)32581-2">South Africa and India</a> are calling on the World Trade Organization to temporarily waive intellectual property rights related to COVID-19 products and treatments. The aim is to be sure that that medicines, vaccines and other technologies needed to control the pandemic can be made available to all. The pharmaceutical industry is opposed to this proposal.</p>
<figure class="align-center ">
<img alt="Gloved hands holding a vial of vaccine" src="https://images.theconversation.com/files/373789/original/file-20201209-16-1f9bd91.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/373789/original/file-20201209-16-1f9bd91.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=402&fit=crop&dpr=1 600w, https://images.theconversation.com/files/373789/original/file-20201209-16-1f9bd91.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=402&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/373789/original/file-20201209-16-1f9bd91.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=402&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/373789/original/file-20201209-16-1f9bd91.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=505&fit=crop&dpr=1 754w, https://images.theconversation.com/files/373789/original/file-20201209-16-1f9bd91.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=505&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/373789/original/file-20201209-16-1f9bd91.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">
<figcaption>
<span class="caption">A vial of the Pfizer-BioNTech COVID-19 vaccine at the Royal Victoria Hospital, in Belfast, Dec. 8, 2020. The United Kingdom has begun its vaccination campaign.</span>
<span class="attribution"><span class="source">(Liam McBurney/Pool via AP)</span></span>
</figcaption>
</figure>
<p>Companies argue that they are already taking voluntary actions that make this move unnecessary. <a href="https://healthpolicy-watch.news/77521-2/">Moderna is not going to enforce its COVID-19-related patents</a> against other companies “while the pandemic continues,” and is willing to license its intellectual property for COVID-19 vaccines for the post-pandemic period. </p>
<p><a href="https://investors.modernatx.com/news-releases/news-release-details/statement-moderna-intellectual-property-matters-during-covid-19">A company statement said</a>, “We feel a special obligation under the current circumstances to use our resources to bring this pandemic to an end as quickly as possible.” But as <a href="https://theconversation.com/covid-19-drug-and-vaccine-patents-are-putting-profit-before-people-149270">Ron Labonte and Mira Johri wrote in <em>The Conversation</em></a>, this is a one-time deal and has “the aura of charity rather than of obligation.”</p>
<p><a href="https://doi.org/10.1016/S0140-6736(20)32581-2">Others opposed to the waiver</a> argue that it would be much quicker to pressure companies to allow non-exclusive licences and technology transfer of their products. But the AstraZeneca agreement with India’s Serum Institute is only a limited success. The deal lacks transparency about costs, while Pfizer has not shown any sign of licensing or transferring the technology needed to manufacture its patented products. Pfizer’s reply to this criticism is that “a one-size-fits-all model disregards the specific circumstances of each situation, each product and each country.”</p>
<figure class="align-right ">
<img alt="Vials labelled 'COVID-19 Coronavirus Vaccine' lined up in rows." src="https://images.theconversation.com/files/373781/original/file-20201209-14-hgi54z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/373781/original/file-20201209-14-hgi54z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=750&fit=crop&dpr=1 600w, https://images.theconversation.com/files/373781/original/file-20201209-14-hgi54z.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=750&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/373781/original/file-20201209-14-hgi54z.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=750&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/373781/original/file-20201209-14-hgi54z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=943&fit=crop&dpr=1 754w, https://images.theconversation.com/files/373781/original/file-20201209-14-hgi54z.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=943&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/373781/original/file-20201209-14-hgi54z.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=943&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The arrival of a COVID-19 vaccine may have boosted public approval of pharmaceutical companies.</span>
<span class="attribution"><span class="source">(Unsplash/Daniel Schludi)</span></span>
</figcaption>
</figure>
<p>So far, no pharmaceutical company has contributed to the <a href="https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novel-coronavirus-2019-ncov/covid-19-technology-access-pool">COVID-19 Technology Access Pool</a>, an initiative backed by the World Health Organization and <a href="https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novel-coronavirus-2019-ncov/covid-19-technology-access-pool/endorsements-of-the-solidarity-call-to-action">endorsed by 40 countries</a> that encourages the voluntary donation of COVID-19 health technology related knowledge, intellectual property and data. The aim of C-TAP is to ensure all populations around the world have access to affordable health products as soon they need them. </p>
<p>Back in May when C-TAP was announced, <a href="https://www.ft.com/content/b964cfb2-5f2e-4cb7-b9ad-535481495eaa">Pfizer CEO Albert Bourla said</a>, “At this point in time, I think it’s nonsense, and … it’s also dangerous,” a remark <a href="https://www.statnews.com/pharmalot/2020/05/28/who-voluntary-pool-patents-pfizer/">echoed by AstraZeneca’s Soriot</a>, who maintained that intellectual property is “a fundamental part of our industry and if you don’t protect IP, then essentially, there is no incentive for anybody to innovate.”</p>
<h2>Private profits, public partners</h2>
<p>Both CEOs have reaped major financial rewards during the pandemic. Between April and August, <a href="https://fortune.com/2020/08/24/oxford-astrazeneca-covid-vaccine-deal-pricing-profit-concerns/">AstraZeneca stock and options owned by Soriot</a> increased by nearly $15 million in value. The day after Pfizer announced promising interim results about its vaccine, <a href="https://www.cnn.com/2020/11/11/investing/pfizer-ceo-albert-bourla-stock-sale-vaccine/index.html">Bourla sold over 130,000 shares of Pfizer stock</a> worth $5.6 million as part of a regularly scheduled plan to periodically sell some of his Pfizer shares.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/as-u-s-buys-up-remdesivir-vaccine-nationalism-threatens-access-to-covid-19-treatments-141952">As U.S. buys up remdesivir, ‘vaccine nationalism’ threatens access to COVID-19 treatments</a>
</strong>
</em>
</p>
<hr>
<p>Finally, it’s important to remember that the drug companies had public partners that provided large amounts of money to accelerate the development of vaccines. </p>
<p><a href="https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-expansion-barda-agreement-support-larger-phase">Moderna received $955 million</a> from the Biomedical Advanced Research and Development Authority and the U.S. government’s Operation Warp Speed initiative. In addition, <a href="https://www.reuters.com/article/us-health-coronavirus-moderna-vaccine-idUSKCN2572T5">Moderna inked a deal</a> with the U.S. government worth $1.5 billion for 100 million doses of its vaccine should it be successful. </p>
<p>Even Pfizer, which did not directly take money from the U.S. government, had a <a href="https://www.latimes.com/business/story/2020-11-09/hiltzik-pfizer-coronavirus-covid19-vaccine-news-encouraging">contract worth $1.95 billion</a> to manufacture 100 million doses of its product if it is effective.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/373782/original/file-20201209-21-arqi2z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="President Donald Trump stands at a podium in front of an Operation Warp Speed banner" src="https://images.theconversation.com/files/373782/original/file-20201209-21-arqi2z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/373782/original/file-20201209-21-arqi2z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/373782/original/file-20201209-21-arqi2z.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/373782/original/file-20201209-21-arqi2z.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/373782/original/file-20201209-21-arqi2z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/373782/original/file-20201209-21-arqi2z.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/373782/original/file-20201209-21-arqi2z.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">President Donald Trump speaks during an Operation Warp Speed Vaccine Summit on the White House complex on Dec. 8, 2020, in Washington.</span>
<span class="attribution"><span class="source">(AP Photo/Evan Vucci)</span></span>
</figcaption>
</figure>
<p>In contrast to Moderna’s earlier altruistic pronouncement, its <a href="https://www.latimes.com/business/story/2020-11-16/who-owns-the-covid-vaccines">CEO Stephane Bancel told investors</a> that “Moderna retains worldwide rights to develop and commercialize [its vaccine] mRNA-1273. Without a corporate partner, Moderna will realize all the profits from our COVID-19 vaccine.… We should have a unique cash position at the end of 2021.” </p>
<p>Despite the injection of money from the U.S. government, the government has no say in Moderna’s manufacturing program.</p>
<p>We should applaud drug companies for developing multiple vaccines in record time, but let’s not be under any illusion about whether a drug company can change. In the end it is profits that are motivating them.</p><img src="https://counter.theconversation.com/content/151739/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>In 2017-2020, Joel Lexchin received payments for being on a panel at the American Diabetes Association, for talks at the Toronto Reference Library, for writing a brief in an action for side effects of a drug for Michael F. Smith, Lawyer and a second brief on the role of promotion in generating prescriptions for Goodmans LLP and from the Canadian Institutes of Health Research for presenting at a workshop on conflict-of-interest in clinical practice guidelines. He is currently a member of research groups that are receiving money from the Canadian Institutes of Health Research and the Australian National Health and Medical Research Council. He is a member of the Foundation Board of Health Action International and the Board of Canadian Doctors for Medicare. He receives royalties from University of Toronto Press and James Lorimer & Co. Ltd. for books he has written. </span></em></p>We should applaud drug companies for developing COVID-19 vaccines in record time, but let’s not be under any illusion about the profits that are motivating them.Joel Lexchin, Professor Emeritus of Health Policy and Management, York University, Emergency Physician at University Health Network, Associate Professor of Family and Community Medicine, University of TorontoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1499472020-11-22T14:16:13Z2020-11-22T14:16:13ZThe mink link: How COVID-19 mutations in animals affect human health and vaccine effectiveness<figure><img src="https://images.theconversation.com/files/370592/original/file-20201120-13-126rzip.jpg?ixlib=rb-1.1.0&rect=57%2C118%2C2292%2C1591&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Mink can be readily infected with SARS-CoV-2 and then pass the virus to humans.
</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>The importance of commercially raised animals in the COVID-19 pandemic has received much attention in the past few weeks, when a <a href="https://www.ecdc.europa.eu/en/publications-data/detection-new-sars-cov-2-variants-mink">new variant</a> of SARS-CoV-2 was detected in farmed mink. Unfortunately, mink tend to be relatively susceptible to respiratory infections, and these can readily spread through <a href="https://fur.ca/fur-farming/mink-farming/">mink farms</a> due to high-density housing. </p>
<p>Data <a href="https://doi.org/10.2807/1560-7917.ES.2020.25.23.2001005">from the Netherlands</a> earlier in the pandemic have revealed that mink can be readily infected with SARS-CoV-2 and then pass the virus to humans. In Denmark, <a href="https://www.who.int/csr/don/06-november-2020-mink-associated-sars-cov2-denmark/en/">214 people</a> people have been infected by a variant of SARS-CoV-2 that is presumed to have mutated in Danish mink. Over <a href="https://www.ecdc.europa.eu/sites/default/files/documents/RRA-SARS-CoV-2-in-mink-12-nov-2020.pdf">200 mink farms</a> had tested positive for SARS-CoV-2, and at least <a href="https://doi.org/10.1136/bmj.m4338">five different mink variants</a> of the virus have been detected so far. </p>
<p>These events initiated a <a href="https://www.sciencemag.org/news/2020/11/mutant-coronaviruses-found-mink-spark-massive-culls-and-doom-danish-group-s-research">mass culling</a> of farmed mink in that country (although this was limited due to <a href="https://www.bbc.com/news/world-europe-54893287">legal issues</a>), and cast a spotlight on the disturbing scenario of <a href="https://science.sciencemag.org/content/early/2020/11/09/science.abe5901">human-to-mink-to-human</a> transmission of SARS-CoV-2, with potential for the virus to change in mink prior to re-infecting people. </p>
<figure class="align-center ">
<img alt="Two white minks in cages" src="https://images.theconversation.com/files/370536/original/file-20201120-17-n92725.jpg?ixlib=rb-1.1.0&rect=109%2C0%2C3075%2C2148&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/370536/original/file-20201120-17-n92725.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=405&fit=crop&dpr=1 600w, https://images.theconversation.com/files/370536/original/file-20201120-17-n92725.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=405&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/370536/original/file-20201120-17-n92725.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=405&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/370536/original/file-20201120-17-n92725.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=509&fit=crop&dpr=1 754w, https://images.theconversation.com/files/370536/original/file-20201120-17-n92725.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=509&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/370536/original/file-20201120-17-n92725.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=509&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Mink are semi-aquatic mammals that are relatively susceptible to respiratory infections, which can spread through mink farms, like this one in Belarus, due to high-density housing.</span>
<span class="attribution"><span class="source">(AP Photo/Sergei Grits, File)</span></span>
</figcaption>
</figure>
<p>Specifically, this latest occurrence unveils the possibility that mink can serve as an alternate host to promote mutations of SARS-CoV-2, which can be passed back to humans and other animals, both domestic and wild and potentially placing the wild mustelid (minks, ferrets and related species) population at risk. </p>
<h2>Bridging human and animal health</h2>
<p>We are researchers in the fields of virology, immunology and pathology. Our research programs bridge human and animal health and study the transmission of viruses, immune responses to viruses, how viruses cause diseases, and developing strategies such as vaccines to prevent infectious diseases. <a href="https://www.who.int/csr/don/06-november-2020-mink-associated-sars-cov2-denmark/en/">The recent news</a> linking mink to the current pandemic highlights the importance of research at the interface of animal and human health.</p>
<p>Since the start of the <a href="https://www.who.int/health-topics/coronavirus#tab=tab_1">COVID-19 pandemic</a>, the world has learned much about virology, as well as the concept of <a href="https://www.cdc.gov/onehealth/basics/index.html">One Health</a>. At the core of One Health is the idea that human and animal health are intertwined in a shared environment, and that we need to broaden our perspectives beyond human health alone. </p>
<p>Indeed, animals have been at the centre of this pandemic from the beginning. Overwhelming evidence suggests that this coronavirus (<a href="https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/naming-the-coronavirus-disease-(covid-2019)-and-the-virus-that-causes-it">SARS-CoV-2</a>), which causes COVID-19, originated <a href="https://doi.org/10.1016/S1473-3099(20)30641-1">from bats</a>. There is debate about whether an intermediate animal host might have harboured additional changes to SARS-CoV-2 to produce the current virus that spreads efficiently person to person. The leading candidate for this is a scaly anteater known <a href="https://doi.org/10.1038/s41586-020-2169-0">as a pangolin</a>. </p>
<figure class="align-center ">
<img alt="A pangolin emerging from a grassy area." src="https://images.theconversation.com/files/370538/original/file-20201120-13-11qx9s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/370538/original/file-20201120-13-11qx9s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=404&fit=crop&dpr=1 600w, https://images.theconversation.com/files/370538/original/file-20201120-13-11qx9s.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=404&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/370538/original/file-20201120-13-11qx9s.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=404&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/370538/original/file-20201120-13-11qx9s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=508&fit=crop&dpr=1 754w, https://images.theconversation.com/files/370538/original/file-20201120-13-11qx9s.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=508&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/370538/original/file-20201120-13-11qx9s.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=508&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The pangolin, a scaly anteater, may have been an intermediate host for the SARS-CoV-2 virus.</span>
<span class="attribution"><span class="source">(AP Photo/Themba Hadebe)</span></span>
</figcaption>
</figure>
<p>What is known for sure is that changes to coronaviruses can occur over time due to inherent and <a href="https://doi.org/10.1371/journal.ppat.1006254">purposeful errors</a> in these viruses’ ability to copy their genetic codes. This allows a virus to make small changes over time and is an efficient way for them to adapt to new environments.</p>
<h2>Changes in the spike protein</h2>
<p>One of the recently identified Danish mink strains is particularly concerning because changes in the genome occurred in what is called the virus’s <a href="https://doi.org/10.1038/s41401-020-0485-4">spike protein</a>, which it uses to enter human cells. These changes have been detected in <a href="https://www.euro.who.int/en/countries/denmark/news/news/2020/11/mink-strain-of-covid-19-virus-in-denmark">12 human cases</a> related to this particular mink variant. Fortunately, this change does not seem to correlate with worse <a href="https://www.nature.com/articles/d41586-020-03218-z">clinical outcomes</a>, based on a small number of cases. </p>
<p>The <a href="https://www.nih.gov/news-events/nih-research-matters/novel-coronavirus-structure-reveals-targets-vaccines-treatments">spike protein</a> is also the primary target of natural and vaccine-induced immune responses to the virus. In theory, if SARS-CoV-2 mutates too much, the immunity derived from the parental virus, acquired either by natural infection or vaccination, could become less effective against the new strain. </p>
<figure class="align-center ">
<img alt="A model of a spike protein in the foreground with the model of the virus in the background" src="https://images.theconversation.com/files/370568/original/file-20201120-23-4v2re9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/370568/original/file-20201120-23-4v2re9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/370568/original/file-20201120-23-4v2re9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/370568/original/file-20201120-23-4v2re9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/370568/original/file-20201120-23-4v2re9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/370568/original/file-20201120-23-4v2re9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/370568/original/file-20201120-23-4v2re9.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">
<figcaption>
<span class="caption">3D print of a spike protein of SARS-CoV-2, the virus that causes COVID-19, in front of a 3D print of a SARS-CoV-2 virus particle. 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>The good news is that, so far, there’s no evidence that the mink-derived SARS-CoV-2 mutant can bypass natural or vaccine-induced immunity. Fortunately, our immune systems are designed to generate antibodies against multiple parts of the spike protein. This means that if only a small part of the spike protein is mutated, antibodies against other parts of the protein should still confer at least some protection. </p>
<h2>‘Plug-and-play’ vaccine technology</h2>
<p>The fact that SARS-CoV-2 can change highlights the need for vaccines that not only induce protective antibodies but that can also elicit robust T cell responses, which is the other major mechanism by which our immune systems can kill viruses. Like antibodies, T cells will target multiple parts of viral proteins, thereby increasing the chance of maintaining immunity against non-mutated regions of the proteins. </p>
<p>It might also be important to consider making vaccines that target more than one of the proteins from SARS-CoV-2. It’s very difficult for a virus to make major changes to multiple proteins without compromising its fitness. </p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/training-our-immune-systems-why-we-should-insist-on-a-high-quality-covid-19-vaccine-146650">Training our immune systems: Why we should insist on a high-quality COVID-19 vaccine</a>
</strong>
</em>
</p>
<hr>
<p>The other issue that the mink SARS-CoV-2 brings to the forefront of the vaccine development effort is the need for vaccines that are “plug-and-play.” These are vaccine technologies where the viral protein the vaccine is designed to target can be readily swapped with a different version of the viral protein. </p>
<p>Once approved by health regulators as being safe and efficacious against a highly pathogenic coronavirus, such technologies could, in theory, be rapidly modified to target emerging mutant viruses; akin to the annual flu vaccine that gets modified every year to target emerging <a href="https://www.cdc.gov/flu/prevent/vaccine-selection.htm">influenza virus variants</a>.</p>
<h2>Addressing threats and managing health</h2>
<p>With mink being confirmed only recently as a possible reservoir for SARS-CoV-2, more research is urgently needed to inform rationally based decisions to cull millions of these animals. Even if mass cullings continue, it is unlikely that mink farms will be completely phased out at the global level in the near future. So the question becomes how do we manage the potential threat to human health of SARS-CoV-2 in mink over the long term? </p>
<p>First, enhanced <a href="http://www.omafra.gov.on.ca/english/livestock/vet/facts/04-003.htm">biosecurity</a> measures should be implemented on mink farms. </p>
<figure class="align-center ">
<img alt="A mink with pale fur on top of a cage, indoors. A human hand is holding its tail." src="https://images.theconversation.com/files/370584/original/file-20201120-23-1wwwybv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/370584/original/file-20201120-23-1wwwybv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/370584/original/file-20201120-23-1wwwybv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/370584/original/file-20201120-23-1wwwybv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/370584/original/file-20201120-23-1wwwybv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/370584/original/file-20201120-23-1wwwybv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/370584/original/file-20201120-23-1wwwybv.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">Farmed mink, like this one from an Ontario fur farm, should be screened for coronaviruses.</span>
<span class="attribution"><span class="source">THE CANADIAN PRESS/ Geoff Robins</span></span>
</figcaption>
</figure>
<p>Second, screening of farmed mink for coronaviruses should be added to the <a href="https://www.inspection.gc.ca/science-and-research/our-laboratories/cahsn/eng/1524146875354/1524146966702">surveillance programs</a> of animal health regulatory agencies, with this information made available to human health regulators. </p>
<p>Third, consideration could be given to tailoring COVID-19 vaccines for animal reservoirs, which would now include farmed mink. These recommendations would not only reduce the potential spread of coronaviruses from mink to humans, it would simultaneously address SARS-CoV-2-related health issues for mink. Indeed, <a href="https://doi.org/10.1177/0300985820943535">mink can develop COVID-19</a> after becoming infected with SARS-CoV-2 and it can sometimes be severe and lethal, with no effective current treatment.</p>
<p>Unless future evidence suggests otherwise, it may be best to stay the course with current vaccine development programs with the goal of getting multiple technological platforms approved for use in humans. Then these platforms can be readily modified, akin to the annual influenza vaccine, to target emerging mutant viruses, if warranted. </p>
<p>Simultaneously, public health agencies with any interest in promoting human health should expand their visions to include the health and surveillance of domestic animals and wildlife at the point where human and veterinary medicine interface. </p>
<p>In the case of SARS-CoV-2, humans are currently the largest reservoir of the virus on Earth, and the threat of spillover from human hosts to farmed animals and wildlife species is now made evident. This is an opportune time to take stock in our relationships with animals and the natural world and take action to ensure health for all and this biosphere we share.</p><img src="https://counter.theconversation.com/content/149947/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Byram Bridle received funding from the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada, the Canada Foundation for Innovation, and Ontario COVID-19 Rapid Research Funding.</span></em></p><p class="fine-print"><em><span>Leonardo Susta received funding from the Natural Sciences and Engineering Research Council of Canada, the Canada Foundation for Innovation, the Ontario COVID-19 Rapid Research Funding, and the Ontario Ministry of Agriculture and Rural Affairs. </span></em></p><p class="fine-print"><em><span>Samira Mubareka receives funding from Natural Sciences and Engineering Research Council of Canada, the Toronto COVID-19 Action Initiative and Genome Canada.</span></em></p><p class="fine-print"><em><span>Shayan Sharif receives funding from Canada First Research Excellence Funds.</span></em></p><p class="fine-print"><em><span>Sarah Wootton 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>In the disturbing scenario of human-to-mink-to-human COVID-19 transmission, the virus may mutate in mink prior to re-infecting people. That possibility makes vaccine design even more crucial.Byram W. Bridle, Associate Professor of Viral Immunology, Department of Pathobiology, University of GuelphLeonardo Susta, Associate professor, Pathobiology, University of GuelphSamira Mubareka, Clinician-scientist, Laboratory Medicine and Pathobiology, University of TorontoSarah Wootton, Associate Professor, Pathobiology, Ontario Veterinary College, University of GuelphShayan Sharif, Professor of Immunology and Associate Dean, Research and Graduate Studies, University of GuelphLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1499352020-11-16T17:15:26Z2020-11-16T17:15:26ZModerna follows Pfizer with exciting vaccine news – how to read these dramatic developments<figure><img src="https://images.theconversation.com/files/369766/original/file-20201117-23-azxflt.jpg?ixlib=rb-1.1.0&rect=108%2C201%2C4795%2C3142&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/selective-focus-end-syringe-while-needle-556416004">DonyaHHI/Shutterstock</a></span></figcaption></figure><p>It is very exciting to hear another positive story about vaccine trial results – a good vaccine is the most likely way of ending the pandemic. </p>
<p>Last week, interim results from Pfizer suggested its vaccine reduces cases of COVID-19 with <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-announce-vaccine-candidate-against">90% efficacy</a>. Now Moderna has gone one better, with interim results showing nearly <a href="https://investors.modernatx.com/news-releases/news-release-details/modernas-covid-19-vaccine-candidate-meets-its-primary-efficacy">95% efficacy</a> for its vaccine – with hints that it may protect against severe disease. Neither have reported any serious safety concerns and have tested their vaccines in tens of thousands of participants.</p>
<p>With so many <a href="https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines">COVID-19 vaccines in development</a>, more results are likely to follow in the coming months. Their headline figures may, like these, be very impressive, but it’s necessary to dig deeper to find out exactly what any new results mean. </p>
<p>With that in mind, here are six questions to ask about any new vaccine trial result.</p>
<h2>1. Does this mean the vaccine is safe?</h2>
<p>Almost certainly yes if it has successfully passed through a phase 3 trial with thousands of participants. Vaccines do not get this far if there are any major doubts about safety.</p>
<p>Historically, pharmaceutical companies have been able to <a href="https://www.who.int/ictrp/trial_reg/en/">suppress negative results</a>, but it’s now <a href="https://www.hra.nhs.uk/planning-and-improving-research/research-planning/research-registration-research-project-identifiers/">legally required</a> for all trials to post their results so that other scientists can review them. As a consequence the sector is generally far more trusted than it used to be, although we should still be cautious if only interim results are being reported.</p>
<p>Some people are concerned that COVID-19 vaccines have been produced with unprecedented speed; however, the <a href="https://milken-institute-covid-19-tracker.webflow.io/#vaccines_intro">vast majority</a> are based on platform technologies with <a href="https://www.who.int/vaccine_safety/initiative/tech_support/Part-2.pdf">excellent safety profiles</a>. There are a few <a href="https://theconversation.com/how-the-leading-coronavirus-vaccines-work-146969">newer technologies</a> being used, but the clinical trial and regulatory process is extremely rigorous and will pick up the majority of potential complications fairly early on in development. </p>
<p>Of course, it is still difficult to know yet about long-term side-effects, but these are <a href="https://www.cdc.gov/vaccines/vac-gen/side-effects.htm">rare for vaccines</a>, and any risk is normally significantly lower than the risks from getting the disease being vaccinated against.</p>
<h2>2. Do the headline figures reflect what the trial was designed to measure?</h2>
<p>Trials often measure many things, but there is always a single primary research question or objective that a trial has been designed to answer.</p>
<p>Trials will also have several secondary research questions, but answering these is not considered a mark of success. If you test enough different objectives, a few will always be met due to blind chance. Misrepresenting trial data in this way is a form of research misconduct called <a href="https://www.wired.com/story/were-all-p-hacking-now/">p-hacking</a>. You can find out the primary and secondary objectives of any trial by checking a <a href="https://www.clinicaltrials.gov">clinical trial registry</a>.</p>
<p>Again, it is important to consider whether these are interim results. Although such results can be promising – as <a href="https://theconversation.com/pfizer-covid-vaccine-promising-results-heres-what-needs-to-happen-next-149809">Pfizer</a> and <a href="https://www.nih.gov/news-events/news-releases/promising-interim-results-clinical-trial-nih-moderna-covid-19-vaccine">Moderna</a> have shown – they are not guaranteed to be the final result.</p>
<h2>3. Did the trial measure the right thing?</h2>
<p>Determining what counts as a medicine or drug “working” can be quite complicated for many diseases. But for vaccines, the question to ask is quite simple: did people who had the active vaccine get the disease? Any measure that’s more complicated than this (often referred to as a <a href="https://www.cancer.gov/publications/dictionaries/cancer-terms/def/surrogate-endpoint">surrogate outcome</a>) should be treated with caution.</p>
<h2>4. Who was the vaccine tested on?</h2>
<p>Are the results of a trial transferable to the real world? Here it’s important to understand the difference between a population (in this case everyone who can catch COVID-19) and the sample of that population who took part in the trial.</p>
<p>In many cases, trials use two carefully matched (and so comparable) samples in carefully controlled conditions. One is given the vaccine and the other a placebo (such as saline injection or an already developed vaccine for another disease) to control for the effect of participants thinking they have been vaccinated – which <a href="https://www.nature.com/articles/tpj201615">does have an effect</a>.</p>
<p>In phase 1 trials, safety concerns mean that samples are generally made up of young and fit people with few health concerns, who are probably not representative of the overall population. However, as trials progress into later phases and get bigger, researchers try to ensure a more representative sample of the population.</p>
<p>This is why the final-stage (phase 3) trials are so important, as the sample is chosen to represent the population that the vaccine is targeted at. Formal publications of trial results normally provide a table describing who was in the sample, and often efficacy rates for the different groups (broken down by sex, age and so on). Unfortunately, the headline efficacy figure (95% for instance) may not apply evenly across the population.</p>
<p>This is very important for COVID-19, as we know older people are much more vulnerable. We therefore shouldn’t read too much into any results until we can see an age breakdown for efficacy.</p>
<h2>5. Will the vaccine be usable?</h2>
<p>Before we get too excited, some practical questions must be asked. How much will the vaccine cost? Can it be made in bulk? Is it easy to transport and store? And how many boosters will be needed? These logistic problems (for instance, the requirement to be stored and transported at very low temperatures) can easily prevent a new vaccine getting into the clinic.</p>
<figure class="align-center ">
<img alt="A freezer control panel showing -79C." src="https://images.theconversation.com/files/369640/original/file-20201116-13-14vjf02.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/369640/original/file-20201116-13-14vjf02.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/369640/original/file-20201116-13-14vjf02.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/369640/original/file-20201116-13-14vjf02.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/369640/original/file-20201116-13-14vjf02.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/369640/original/file-20201116-13-14vjf02.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/369640/original/file-20201116-13-14vjf02.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">
<figcaption>
<span class="caption">Pfizer’s vaccine needs to be stored at -80C, which will make rolling it out more difficult.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/blur-abstract-background-ultra-low-temperature-674960770">BlurryMe/Shutterstock</a></span>
</figcaption>
</figure>
<h2>6. Can we trust what’s being reported?</h2>
<p>It’s an increasingly important skill to identify between reliable and unreliable sources. Social media is often superficial and prone to spreading misinformation. On the other hand, journal articles and clinical trial registries can be hard to interpret for anyone except specialists.</p>
<p>Trusted journalism is the answer. Seek out publications with editorial oversight and a track record of reliable scientific and medical reporting. Reading more than one interpretation can help you get a balanced view.</p>
<p>It’s also important to ask where a journalist found the information they are reporting on. Referencing results published in peer-reviewed journals is a good sign – it shows some rigorous fact checking has occurred. Be careful if an article’s main sources seem to be <a href="https://theconversation.com/researchers-use-pre-prints-to-share-coronavirus-results-quickly-but-that-can-backfire-137501">preprints</a> (papers not yet peer reviewed) or other so-called <a href="https://library.leeds.ac.uk/info/1110/resource_guides/7/grey_literature">grey literature</a>, such as press releases or company reports. </p>
<p>Likewise, be careful if the main source seems to be interviews or quotes from people with PhDs or impressive sounding job titles. A quote from a scientist in an interview is not equivalent to a quote from the same scientist in a peer-reviewed academic paper.</p><img src="https://counter.theconversation.com/content/149935/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>The recent vaccine trial results certainly look impressive, but here’s how to fully interrogate what they mean.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/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>
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<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>
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<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>
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<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>
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<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>
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<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>
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<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>
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<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>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/how-researchers-assess-whether-medications-work-102773">How researchers assess whether medications work</a>
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<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>
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<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>
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<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/1478812020-10-14T13:56:44Z2020-10-14T13:56:44ZCoronavirus vaccine: what we know so far – a comprehensive guide by academic experts<figure><img src="https://images.theconversation.com/files/363015/original/file-20201012-19-1tzx7w5.jpg?ixlib=rb-1.1.0&rect=0%2C54%2C5912%2C3902&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/bottles-coronavirus-vaccine-sarscov2-covid19-some-1673662414">M-Foto/Shutterstock</a></span></figcaption></figure><p>Since the early days of the pandemic, attention has focused on producing a vaccine for COVID-19. With one, it’s hoped it will be able to suppress the virus without relying purely on economically challenging control measures. Without one, the world will probably have to live with COVID-19 as an endemic disease. It’s <a href="https://theconversation.com/the-original-sars-virus-disappeared-heres-why-coronavirus-wont-do-the-same-138177">unlikely</a> the coronavirus will naturally burn itself out.</p>
<p>With so much at stake, it’s not surprising that COVID-19 vaccines have become both a public and political obsession. The good news is that <a href="https://theconversation.com/coronavirus-vaccine-reasons-to-be-optimistic-137209">making one is possible</a>: the virus has the right characteristics to be fended off with a vaccine, and the economic incentive exists to get one (or indeed several) developed.</p>
<p>But we need to be patient. Creating a new medicine requires a large amount of <a href="https://theconversation.com/dont-hold-your-breath-for-a-covid-19-vaccine-in-2020-137441">thought and scrutiny</a> to make sure what’s produced is safe and effective. Researchers must be careful not to allow the pressure and allure of creating a vaccine quickly to undermine the integrity of their work. The upshot may be that we don’t have a highly effective vaccine against COVID-19 for some time. </p>
<p>Here, authors from across The Conversation outline what we know so far. Drawing upon their expertise, they explain how a COVID-19 vaccine will work, the progress a leading vaccine (developed by the University of Oxford with AstraZeneca) is making, and what challenges there will be to manufacturing and rolling a vaccine out when ready. </p>
<p><strong>How will vaccines work for COVID-19?</strong> <br>
<a href="#spikeprotein">How the spike protein is produced</a><br>
<a href="#differentdesigns">The benefits of different designs</a><br>
<a href="#boosters">Why boosters may be needed</a><br>
<a href="#howwerespond">What determines how we respond to vaccines</a><br>
<a href="#vaccineimmunity">Why vaccines provide strong immunity</a><br>
<a href="#howtousevaccine">How to use a vaccine when it’s available</a><br></p>
<p><strong>How is the Oxford vaccine being developed, tested and approved?</strong> <br>
<a href="#steps">The many steps of vaccine development</a><br>
<a href="#phase1and2">The results of phase 1 and phase 2 trials</a><br>
<a href="#phase2">How the phase 3 trial will work</a><br>
<a href="#testingpaused">Why testing was paused – and why we shouldn’t be alarmed</a><br>
<a href="#open">Why vaccine makers need to be more open</a><br>
<a href="#placebos">Why we need to know what’s in placebos</a><br></p>
<p><strong>How will the vaccine be made and rolled out?</strong> <br>
<a href="#preparing">How to prepare enough vaccines for the whole world</a><br>
<a href="#tobacco">How tobacco could play a role in producing a vaccine</a><br>
<a href="#coldchain">Why vaccines need to be kept cold</a><br>
<a href="#vaccinenationalism">Will rich countries buy up the supply when vaccines are available?</a><br>
<a href="#counteringnationalism">How to stop rich countries from depriving poorer ones</a><br>
<a href="#whogetsvaccinesfirst">Who should get a vaccine first?</a><br></p>
<p><strong>How do you counter resistance and scepticism?</strong> <br>
<a href="#resistance">Vaccine hesitancy is nothing new</a><br>
<a href="#antivaxxers">Are anti-vaxxers that big a problem?</a><br>
<a href="#farright">How the far right is exploiting the pandemic</a><br>
<a href="#trust">How to build trust in vaccines</a><br></p>
<hr>
<h2>How will vaccines work for COVID-19?</h2>
<p></p><p id="spikeprotein"><b>Producing the spike protein</b></p> Although the way the body interacts with SARS-CoV-2 isn’t fully understood, there’s one particular part of the virus that’s thought to trigger an immune response – the spike protein, which sticks up on the virus’s surface. Therefore, the two leading COVID-19 vaccines both focus on getting the body to <a href="https://theconversation.com/how-the-leading-coronavirus-vaccines-work-146969">produce these key spike proteins</a>, to train the immune system to recognise them and destroy any viral particles that exhibit them in the future.<p></p>
<figure class="align-center ">
<img alt="Illustration of the SARS-CoV-2, showing the spike proteins on its surface" src="https://images.theconversation.com/files/348153/original/file-20200717-25-1v585an.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/348153/original/file-20200717-25-1v585an.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=602&fit=crop&dpr=1 600w, https://images.theconversation.com/files/348153/original/file-20200717-25-1v585an.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=602&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/348153/original/file-20200717-25-1v585an.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=602&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/348153/original/file-20200717-25-1v585an.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=757&fit=crop&dpr=1 754w, https://images.theconversation.com/files/348153/original/file-20200717-25-1v585an.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=757&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/348153/original/file-20200717-25-1v585an.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=757&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">SARS-CoV-2, with its spike proteins shown in red.</span>
<span class="attribution"><a class="source" href="https://en.wikipedia.org/wiki/File:SARS-CoV-2_without_background.png">US Centers for Disease Control and Prevention/Wikimedia Commons</a></span>
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</figure>
<p></p><p id="differentdesigns"><b>The pros and cons of different designs</b></p> The leading vaccines both work by delivering a piece of the coronavirus’s genetic material into cells, which instructs the cell to make copies of the spike protein. As Suresh Mahalingam and Adam Taylor <a href="https://theconversation.com/from-adenoviruses-to-rna-the-pros-and-cons-of-different-covid-vaccine-technologies-145454">explain</a>, one (Moderna’s) makes the delivery using a molecule called messenger RNA, the other (AstraZeneca’s) using a harmless adenovirus. These cutting-edge vaccine designs have their pros and cons, as do traditional methods.<p></p>
<p></p><p id="boosters"><b>Boosters may be needed</b></p> The <a href="https://theconversation.com/a-coronavirus-vaccine-may-require-boosters-heres-what-that-means-143370">strongest immune responses</a>, says Sarah Pitt, come from vaccines that contain a live version of what they’re trying to protect against. Because there’s so much we don’t know about SARS-CoV-2, putting a live version of the virus into a vaccine can be risky. Safer methods – such as getting the body to make just the virus’s spike proteins, or delivering a dead version of the virus – will lead to a weaker response that fades over time. But boosters can top this up.<p></p>
<p></p><p id="howwerespond"><b>What governs how we respond to vaccines?</b></p> A vaccine’s design isn’t the only factor that determines how strong our immune response is. As Menno van Zelm and Paul Gill show, there are <a href="https://theconversation.com/5-ways-our-immune-responses-to-covid-vaccines-are-unique-145248">four other variables</a> that make each person’s response to a vaccine unique: their age, their genes, lifestyle factors and what previous infections they have been exposed to. It may be that not everyone gets long-lasting immunity from a vaccine.<p></p>
<p></p><p id="vaccineimmunity"><b>Why vaccines provide strong immunity</b></p> If well-designed, a vaccine can provide <a href="https://theconversation.com/why-a-vaccine-can-provide-better-immunity-than-an-actual-infection-145476">better immunity</a> than natural infection, says Maitreyi Shivkumar. This is because vaccines can focus the immune system on targeting recognisable parts of the pathogen (for example the spike protein), can kickstart a stronger response using ingredients called adjuvants, and can be delivered to key parts of the body where an immune response is needed most. For COVID-19, this could be the nose.<p></p>
<figure class="align-center ">
<img alt="A woman receiving a nasal flu vaccine." src="https://images.theconversation.com/files/363020/original/file-20201012-21-1wjtmii.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/363020/original/file-20201012-21-1wjtmii.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/363020/original/file-20201012-21-1wjtmii.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/363020/original/file-20201012-21-1wjtmii.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/363020/original/file-20201012-21-1wjtmii.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/363020/original/file-20201012-21-1wjtmii.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/363020/original/file-20201012-21-1wjtmii.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=502&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Nasally delivered vaccines are already in use for some diseases, such as flu.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:14234CDC_Flumist.tif">Douglas Jordan, MA/CDC</a></span>
</figcaption>
</figure>
<p></p><p id="howtousevaccine"><b>How to use a vaccine when it’s available</b></p> Scientists think between 50% and 70% of people need to be resistant to the coronavirus to stop it spreading. Using a vaccine to rapidly make that many people immune might be difficult, says Adam Kleczkowski. Vaccines are rarely 100% effective, and hesitancy and potential side effects may make a quick, mass roll-out unrealistic. A <a href="https://theconversation.com/coronavirus-how-to-use-a-vaccine-when-it-becomes-available-135113">better strategy</a> might be to target people most at risk together with those likely to infect many others.<p></p>
<hr>
<h2>How is the Oxford vaccine being developed, tested and approved?</h2>
<p></p><p id="steps"><b>The many steps of vaccine development</b></p> Vaccine development is quicker now than it ever has been, explain Samantha Vanderslott, Andrew Pollard and Tonia Thomas. Researchers can use knowledge from previous vaccines, and in an outbreak more resources are made available. Nevertheless, it’s still a <a href="https://theconversation.com/coronavirus-vaccine-here-are-the-steps-it-will-need-to-go-through-during-development-134726">lengthy process</a>, involving research on the virus, testing in animals and clinical trials in humans. Once approved, millions of doses then need to be produced.<p></p>
<p></p><p id="phase1and2"><b>Phase 1 and phase 2 trials are successful</b></p> After showing promise in animals, the University of Oxford’s vaccine moved onto human testing – known as clinical trials, which are split into three phases. Here, Rebecca Ashfield outlines the joint phase 1 and 2 trial that the vaccine passed through to check that it was <a href="https://theconversation.com/oxford-immunologist-on-coronavirus-vaccine-our-early-results-look-highly-promising-141558">safe and elicited an immune response</a>, and explains how the vaccine actually uses a separate virus – a chimpanzee adenovirus – to deliver its content into cells. <p></p>
<p></p><p id="phase3"><b>How the phase 3 trial works</b></p> Earlier trial phases showed that the vaccine stimulated the immune system, as expected. But the million-dollar question is whether this actually protects against COVID-19. Finding out means giving the vaccine to <a href="https://theconversation.com/oxford-scientists-these-are-final-steps-were-taking-to-get-our-coronavirus-vaccine-approved-144623">thousands of people</a> who might be exposed to the coronavirus and seeing whether they get sick. As Ashfield and Pedro Folegatti show, this requires running vaccination programmes in countries across the world.<p></p>
<p></p><p id="testingpaused"><b>Testing was paused – and that’s OK</b></p> In September, the phase 3 trial of the Oxford vaccine was paused after a patient fell ill with a possible adverse reaction. Understandably this caused dismay, but it shouldn’t have, says Simon Kolstoe. <a href="https://theconversation.com/the-oxford-vaccine-trial-has-been-paused-but-this-is-no-reason-to-panic-145882">Pauses like this are common</a>, as independent moderators are needed to assess exactly what has happened. Often illnesses in trials are unrelated to what’s being tested. But even if they are, that’s exactly what we want these tests to show.<p></p>
<figure class="align-center ">
<img alt="A person receiving an injection in their arm." src="https://images.theconversation.com/files/357276/original/file-20200909-14-wlouuc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/357276/original/file-20200909-14-wlouuc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/357276/original/file-20200909-14-wlouuc.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/357276/original/file-20200909-14-wlouuc.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/357276/original/file-20200909-14-wlouuc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/357276/original/file-20200909-14-wlouuc.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/357276/original/file-20200909-14-wlouuc.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">In the US arm of the trial, one-third of participants are receiving a saline injection as a control.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/selective-focus-end-syringe-while-needle-556416004">DonyaHHI/Shutterstock</a></span>
</figcaption>
</figure>
<p></p><p id="open"><b>But vaccine makers need to be more open</b></p> AstraZeneca didn’t publicly reveal what caused the pause but did share this information with investors. This, says Duncan Matthews, was an example of an attempt to <a href="https://theconversation.com/why-astrazeneca-and-others-racing-to-make-a-covid-19-vaccine-should-be-more-open-about-the-process-146057">apply old methods of operating to a new situation</a>. <p></p>
<p></p><p id="placebos"><b>Why we need to know what’s in placebos</b></p> A key part of clinical trials are placebos – alternative or inactive treatments that are given to participants for comparison. But a <a href="https://theconversation.com/coronavirus-vaccine-why-its-important-to-know-whats-in-the-placebo-146365">key problem</a>, Jeremy Howick explains, is that some vaccine trials don’t reveal what their placebos contain. Without knowing what benchmark is being used, it’s then difficult for outsiders to understand the relative effect (and side effects) the vaccine has.<p></p>
<hr>
<h2>How will the vaccine be made and rolled out?</h2>
<p></p><p id="preparing"><b>Preparing enough for the whole world</b></p> Universal demand for a COVID-19 vaccine means production bottlenecks are a risk. For the Oxford vaccine, production involves growing key components in human embryonic kidney cells, before creating the actual vaccine and then purifying and then concentrating it. Running this process at industrial scale, say Qasim Rafiq and Martina Micheletti, is one of the <a href="https://theconversation.com/coronavirus-vaccine-search-how-were-preparing-to-make-enough-for-the-whole-world-137970">biggest challenges</a> AstraZeneca faces.<p></p>
<figure class="align-center ">
<img alt="A woman working in a vaccine manufacturing plant." src="https://images.theconversation.com/files/334702/original/file-20200513-156629-16e8k91.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/334702/original/file-20200513-156629-16e8k91.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/334702/original/file-20200513-156629-16e8k91.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/334702/original/file-20200513-156629-16e8k91.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/334702/original/file-20200513-156629-16e8k91.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/334702/original/file-20200513-156629-16e8k91.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/334702/original/file-20200513-156629-16e8k91.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">
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<span class="caption">AstraZeneca and its partners are aiming to manufacture 2 billion doses of its vaccine by the end of 2021.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/pharmaceutical-factory-worker-wearing-protective-work-573090097">RGtimeline/Shutterstock</a></span>
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<p></p><p id="tobacco"><b>Tobacco – an unexpected ally?</b></p> Vaccines contain organic products, which traditionally have been grown using cell cultures in containers called bioreactors. Recently plants have been adapted to function as bioreactors too, which could help production be massively increased. Tobacco may be <a href="https://theconversation.com/pharming-for-a-vaccine-the-answer-to-coronavirus-may-be-in-tobacco-plants-138496">especially useful</a>: it grows quickly, is farmed all over the world, is leafy and easily modifiable. The tech hasn’t been approved for mass producing medicines – but demand may change that. <p></p>
<p></p><p id="coldchain"><b>Keeping vaccines cool will be crucial</b></p> Because COVID-19 vaccines will contain biological material, they’ll need to be <a href="https://theconversation.com/keeping-coronavirus-vaccines-at-subzero-temperatures-during-distribution-will-be-hard-but-likely-key-to-ending-pandemic-146071">kept cold</a> right up until they’re delivered, explains Anna Nagurney. Fail to keep them cool and they’ll become ineffective. Refrigeration will therefore be a major challenge in any roll-out campaign; an estimated 25% of vaccines are spoiled by the time they reach their destination. A <a href="https://theconversation.com/vaccines-often-degrade-in-the-heat-heres-how-our-new-chemical-casing-could-save-lives-118361">potential solution</a> could be to encase their heat-sensitive parts in silica.<p></p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/358707/original/file-20200917-20-xfmbe6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A man in a lab coat stands in front of a freezer filled with medical supplies." src="https://images.theconversation.com/files/358707/original/file-20200917-20-xfmbe6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/358707/original/file-20200917-20-xfmbe6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/358707/original/file-20200917-20-xfmbe6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/358707/original/file-20200917-20-xfmbe6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/358707/original/file-20200917-20-xfmbe6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/358707/original/file-20200917-20-xfmbe6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/358707/original/file-20200917-20-xfmbe6.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>
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<span class="caption">Cold storage facilities will be needed to store vaccines, while refrigerated trucks and planes will be needed to move them.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/lab-technicians-takes-reagents-from-cold-storage-at-lancet-news-photo/1158351596?adppopup=true">Tony Karumba/AFP via Getty Images</a></span>
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<p></p><p id="vaccinenationalism"><b>‘Vaccine nationalism’ threatens universal access</b></p> Some governments are <a href="https://theconversation.com/why-vaccine-nationalism-could-doom-plan-for-global-access-to-a-covid-19-vaccine-145056">signing agreements with manufacturers</a> to supply them with vaccines ahead of other countries. Poorer nations risk being left empty handed – putting people at risk and preventing any attempt to coordinate suppressing the coronavirus worldwide. It’s also unclear how <a href="https://theconversation.com/coronavirus-how-countries-aim-to-get-the-vaccine-first-by-cutting-opaque-supply-deals-143366">access is being priced</a> in these deals.<p></p>
<p></p><p id="counteringnationalism"><b>How to counter vaccine nationalism</b></p> India can play a key role in avoiding this “richest-takes-all” scenario, says Rory Horner. It’s traditionally been a <a href="https://theconversation.com/india-is-key-for-global-access-to-a-covid-19-vaccine-heres-why-144772">major supplier of medicines</a> to the global south, and has the capacity to create more vaccines for COVID-19 than any other country in the world. India’s Serum Institute has signed up to make 400 million doses of the Oxford vaccine this year, but with a population of 1.35 billion, how many will go abroad isn’t yet clear.<p></p>
<figure class="align-center ">
<img alt="Mumbai medical worker prepares a vaccine" src="https://images.theconversation.com/files/354390/original/file-20200824-22-j0bwwb.jpg?ixlib=rb-1.1.0&rect=371%2C112%2C5007%2C3332&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/354390/original/file-20200824-22-j0bwwb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/354390/original/file-20200824-22-j0bwwb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/354390/original/file-20200824-22-j0bwwb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/354390/original/file-20200824-22-j0bwwb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/354390/original/file-20200824-22-j0bwwb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/354390/original/file-20200824-22-j0bwwb.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">
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<span class="caption">India’s track record in producing vaccines and key medical ingredients has led to it being labelled the ‘pharmacy of the world’.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/mumbaiindia-june-23-2020-medical-worker-1769187953">Shutterstock/ManoejPaateel</a></span>
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<p></p><p id="whogetsvaccinesfirst"><b>Who will get the coronavirus vaccine first?</b></p> We need to plan now, say Laurence Roope and Philip Clarke. Governments have big decisions to make. The pandemic is akin to a war situation, so there’s an argument these vital goods should be rationed and banned from private sale. Authorities also need to decide <a href="https://theconversation.com/who-will-get-the-coronavirus-vaccine-first-we-need-to-plan-now-144986">who should be prioritised</a>: those most vulnerable, people most likely to spread the virus, or those who can kickstart the economy by returning to work. <p></p>
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<h2>How do you counter resistance and scepticism?</h2>
<p></p><p id="resistance"><b>Public resistance is a sizeable problem – but nothing new</b></p> Surveys show that <a href="https://theconversation.com/survey-shows-1-in-4-new-zealanders-remain-hesitant-about-a-coronavirus-vaccine-145304">one in four New Zealanders</a> remain hesitant about a coronavirus vaccine, while <a href="https://theconversation.com/coronavirus-anti-vaxxers-one-in-six-british-people-would-refuse-a-vaccine-heres-how-to-change-their-minds-142207">one in six British people</a> would refuse one. But vaccine hesitancy <a href="https://theconversation.com/from-cowpox-to-mumps-people-have-always-had-a-problem-with-vaccination-131530">has been around for a long time</a>, writes Sally Frampton. And Steven King argues <a href="https://theconversation.com/coronavirus-vaccine-lessons-from-the-19th-century-smallpox-anti-vaxxer-movement-143375">the past</a> – such as when smallpox vaccines were resisted – may provide some solutions to this problem.<p></p>
<p></p><p id="antivaxxers"><b>Are anti-vaxxers a problem?</b></p> Not all hesitancy is the same, <a href="https://theconversation.com/coronavirus-the-three-types-of-vaccine-hesitancy-authorities-need-to-combat-146730">says Annamaria Carusi</a>. As well as the hardcore anti-vaxxers, plenty may resist COVID-19 vaccines on safety or animal welfare grounds. Indeed, while anti-vaxxers attract a lot of attention, their influence on vaccination rates is <a href="https://theconversation.com/anti-vaxxer-effect-on-vaccination-rates-is-exaggerated-92630">often overstated</a>, argues Samantha Vanderslott. In fact, desire for a vaccine is so widespread and strong that anti-vaxxer positions may be <a href="https://theconversation.com/what-impact-will-the-coronavirus-pandemic-have-on-anti-vaxxers-135153">harder to defend</a> right now. <p></p>
<p></p><p id="farright"><b>The far right is exploiting the pandemic</b></p> A recent report from the United Nations Security Council warned that extreme right-wing groups in the US are using the pandemic to “radicalise, recruit, and inspire plots and attacks”. Blyth Crawford gives a <a href="https://theconversation.com/coronavirus-and-conspiracies-how-the-far-right-is-exploiting-the-pandemic-145968">run-down of the major groups</a> at work in America – what their aims are, the methods they’re using to reach people, and the key pieces of misinformation that they’re peddling.<p></p>
<p></p><p id="trust"><b>How to build trust in vaccines</b></p> The usual strategy is to double down on positive messaging. But a <a href="https://theconversation.com/anti-vaxxers-admitting-that-vaccinology-is-an-imperfect-science-may-be-a-better-way-to-defeat-sceptics-111794">better strategy</a>, Mark Honigsbaum argues, would be to acknowledge that there’s a lot we don’t know about how some vaccines work, but that the benefits of taking vaccines far outweigh the risks. A further step could be to make sure that <a href="https://theconversation.com/big-pharmas-safety-pledge-isnt-enough-to-build-public-confidence-in-covid-19-vaccine-heres-what-will-145822">manufacturers are liable</a> should vaccine recipients suffer negative effects. Often manufacturers are exempt.<p></p>
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<h2>Looking ahead</h2>
<p>The future is full of possibility. COVID-19, Sars, Mers and the common cold are all caused by coronaviruses, and scientists are considering whether it’s possible to create a vaccine that could offer <a href="https://theconversation.com/one-vaccine-to-beat-covid-sars-mers-and-common-cold-possible-141586">protection against them all</a> – and perhaps even against an as yet unknown coronavirus we’re yet to encounter. Admittedly, having a vaccine that can do this seems unlikely in the near future.</p>
<p>We shouldn’t get ahead of ourselves, though, says Sarah Pitt. No vaccine has yet completed its safety trials, and we can’t yet be sure that any vaccine will permanently prevent people from catching COVID-19. We need to prepare ourselves for the <a href="https://theconversation.com/coronavirus-what-will-happen-if-we-cant-produce-a-vaccine-144307">very real possibility</a> that a COVID-19 vaccine only reduces the severity of symptoms or provides temporary protection.</p><img src="https://counter.theconversation.com/content/147881/count.gif" alt="The Conversation" width="1" height="1" />
Experts from across The Conversation look at how COVID-19 vaccines will work, how they’re being tested and manufactured, and what challenges there will be to rolling them out.Rob Reddick, Commissioning Editor, COVID-19Licensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1476532020-10-11T18:58:26Z2020-10-11T18:58:26ZHow patent law and medicine regulations could affect New Zealand’s access to a COVID-19 vaccine<p>New Zealand has allocated an undisclosed sum, in the order of hundreds of millions of dollars, to <a href="https://www.beehive.govt.nz/release/progress-covid-19-vaccine-strategy">access COVID-19 vaccines</a> when they become available.</p>
<p>The funding is on top of a NZ$37 million <a href="https://www.health.govt.nz/our-work/diseases-and-conditions/covid-19-novel-coronavirus/covid-19-current-situation/covid-19-vaccine-strategy">vaccine strategy</a>, but the government has not released specifics because of commercial sensitivities that “could prevent the best possible deal for New Zealanders”.</p>
<p>Apart from the intricacies of global efforts to develop, test and distribute a vaccine, there are also domestic legal issues the government might need to consider, particularly in patent law and the regulatory review of medicines. </p>
<p>Legislative changes to future-proof the law could avoid delays and lower access costs. </p>
<h2>Patent law and access</h2>
<p>Some <a href="https://blogs.bmj.com/medical-ethics/2020/08/04/patents-private-governance-access-to-vaccines-and-treatments-for-covid-19/">fear</a> pharmaceutical companies could <a href="https://blogs.lse.ac.uk/covid19/2020/09/10/could-university-patents-stand-in-the-way-of-universal-global-access-to-a-covid-19-vaccine/">patent a COVID-19 vaccine</a> and hold the world hostage, demanding monopoly prices. </p>
<p>But to get a patent the invention has to be novel and non-obvious. There is possibly enough <a href="https://www.the-scientist.com/news-opinion/journals-open-access-to-coronavirus-resources--67105">public information</a> about vaccines currently under investigation or in trials to make it difficult for a company to prove novelty or non-obviousness.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/whoever-invents-a-coronavirus-vaccine-will-control-the-patent-and-importantly-who-gets-to-use-it-138121">Whoever invents a coronavirus vaccine will control the patent – and, importantly, who gets to use it</a>
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<p>Even if a vaccine were in some way patent-protected in New Zealand, the government is already <a href="https://www.rnz.co.nz/news/national/424556/covid-19-government-allocates-significant-extra-funding-towards-vaccine">negotiating for access</a>. </p>
<p>If the negotiations fail or the prices demanded are too high, New Zealand law allows for <a href="http://www.legislation.govt.nz/act/public/2013/0068/latest/DLM2193523.html">compulsory licensing</a> and <a href="http://www.legislation.govt.nz/act/public/2013/0068/latest/DLM2193530.html">Crown use</a> of patented inventions. Both are also allowed under <a href="https://www.wto.org/english/docs_e/legal_e/27-trips_04c_e.htm#5">international trade law</a>.</p>
<p>At the moment, an application for a <a href="http://www.legislation.govt.nz/act/public/2013/0068/latest/DLM2193523.html">compulsory licence</a> is only possible after negotiations with a patent owner have failed and if three years have lapsed since the patent was granted (or four years since the patent application was filed). But international trade law states that any requirement to negotiate with the patent owner may be waived in the case of a national emergency or other circumstances of extreme urgency.</p>
<p>Parliament should consider amending New Zealand patent law to be clear that, in a national emergency, anyone can apply for a compulsory licence at any point, without the requirement to negotiate with the patent owner first.</p>
<p>Both international and New Zealand law allow pharmaceutical products manufactured under a compulsory licence to be exported to address a serious public health problem in another country. This might prove important for Pacific nations. </p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/why-vaccine-nationalism-could-doom-plan-for-global-access-to-a-covid-19-vaccine-145056">Why 'vaccine nationalism' could doom plan for global access to a COVID-19 vaccine</a>
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<h2>Government emergency access</h2>
<p>Government departments can use patented inventions <a href="http://www.legislation.govt.nz/act/public/2013/0068/latest/DLM2193531.html">for the services of the Crown</a>. This can be delegated, for example, to a local pharmaceutical manufacturing company. </p>
<p>In an emergency, there is no requirement for the Crown to negotiate a licence with the patent owner first. Nor does the Crown need to wait for a certain period of time to lapse. </p>
<p>This currently covers protecting New Zealand’s security or defence, or managing a state of emergency. A global pandemic can trigger a state of emergency, as <a href="https://www.beehive.govt.nz/release/state-national-emergency-declared-fight-covid-19">happened in New Zealand</a> in March 2020. But to future-proof the law, parliament should consider amending the definition of “emergency” to specifically include health emergencies.</p>
<p>Crown use provisions would allow the government to make and use any patented vaccine or medicine, and to sell any product in excess to its requirements. This would allow sale to a Pacific nation for a nominal amount.</p>
<h2>A vaccine must be safe</h2>
<p>In contrast to patent protection, there are no exceptions to the regulatory review of medicines. Anyone who wants to distribute, sell or advertise a medicine in New Zealand must have regulatory approval from <a href="https://www.medsafe.govt.nz/">Medsafe</a>. </p>
<p>Applicants must submit <a href="http://www.legislation.govt.nz/act/public/1981/0118/latest/DLM55057.html">information and data</a> about the pharmaceutical and the proposed on-label uses. This includes reports on any tests and clinical trials, and data on safety and efficacy. Medsafe decides whether to approve a medicine based on this information. </p>
<p>The process can be lengthy and could delay access to a vaccine. But parliament could legislate a narrow regulatory review “highway” — if regulatory approval for a vaccine is granted elsewhere, such as the European Union, Australia or Canada, it could automatically get approval in New Zealand. </p>
<p>Other aspects of the regulatory process will determine the cost of a vaccine.</p>
<p>Generic medicines — essentially imitations — make the price of pharmaceuticals competitive. Generic pharmaceutical companies don’t usually generate data or run clinical trials. Instead, they show their product is <a href="https://www.pharmac.govt.nz/medicines/medicines-information/generic-medicines/">equivalent to the original medicine</a> and ask Medsafe to use the original data to determine safety. </p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/creating-a-covid-19-vaccine-is-only-the-first-step-itll-take-years-to-manufacture-and-distribute-144352">Creating a COVID-19 vaccine is only the first step. It'll take years to manufacture and distribute</a>
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<p>But Medsafe is not allowed to use any data it receives for one application for the assessment of another for five years. Any vaccine could become obsolete within five years.</p>
<p>There is an exception allowing Medsafe to use data if it is “necessary to protect the health or safety of members of the public”. One can argue that having competition, lower prices and wide distribution of a COVID-19 vaccine meets this requirement. Parliament should amend the legislation to make this clear. </p>
<p>If we allow generic companies to rely on the data of original innovator companies, there would be at least two entities in the market competing with the same vaccine. </p>
<p>We don’t know what’s coming but that shouldn’t stop us from future-proofing our laws and regulatory processes for the different possibilities. New Zealand needs to take advantage of the flexibilities in international trade law to get a COVID-19 vaccine, possibly even two or three, to New Zealanders as quickly and cheaply as possible.</p><img src="https://counter.theconversation.com/content/147653/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jessica C Lai 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>New Zealand has entered several international agreements to access COVID-19 vaccines, but it should also amend domestic patent law and regulatory processes to prevent delays and costly negotiations.Jessica C Lai, Associate Professor in Commercial Law, Te Herenga Waka — Victoria University of WellingtonLicensed as Creative Commons – attribution, no derivatives.