tag:theconversation.com,2011:/id/topics/csl-715/articlesCSL – The Conversation2021-07-26T19:55:48Ztag:theconversation.com,2011:article/1650012021-07-26T19:55:48Z2021-07-26T19:55:48ZHow Australia’s fickleness on COVID vaccines is perpetuating global vaccine inequity<p>Despite assurances from Prime Minister Scott Morrison that Australia was at “<a href="https://theconversation.com/scott-morrison-to-announce-two-new-covid-vaccine-deals-149458">the front of the queue</a>” for COVID-19 vaccines, Australia’s rate of vaccination ranks <a href="https://www.yourlifechoices.com.au/health/covid19/were-bottom-of-the-oecd-class-in-vaccination-rates/">last in the OECD</a>. </p>
<p>Nevertheless, Australia is still ahead of <a href="https://www.nytimes.com/interactive/2021/world/covid-vaccinations-tracker.html">scores of other nations</a> when it comes to vaccination rates, with many countries in the developing world unlikely to be able to vaccinate significant numbers of their people <a href="https://www.nature.com/articles/d41586-021-01762-w">before 2023</a>. </p>
<p>Global vaccine inequity is a “<a href="https://www.bbc.com/news/world-55709428">catastrophic moral failure</a>”, according to the director-general of the World Health Organization, Tedros Adhanom Ghebreyesus. </p>
<p>But we are too focused on our own situation in Australia to realise the damage our fickle approach to vaccines is doing to global vaccine equity. We are also forgetting our human rights obligations to help speed up access to vaccines for all. </p>
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<img alt="" src="https://images.theconversation.com/files/413075/original/file-20210726-15-18a9gap.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/413075/original/file-20210726-15-18a9gap.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/413075/original/file-20210726-15-18a9gap.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/413075/original/file-20210726-15-18a9gap.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/413075/original/file-20210726-15-18a9gap.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/413075/original/file-20210726-15-18a9gap.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/413075/original/file-20210726-15-18a9gap.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">South Africa is averaging over 10,000 new cases per day, yet has only fully vaccinated about 4% of its population.</span>
<span class="attribution"><span class="source">Alet Pretorius/AP</span></span>
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<h2>Vaccine access and international human rights law</h2>
<p>Australia has international human rights obligations to protect the <a href="https://www.ohchr.org/en/professionalinterest/pages/cescr.aspx">health</a> and <a href="https://www.ohchr.org/en/professionalinterest/pages/ccpr.aspx">life</a> of its own people. This means taking reasonable steps to prevent COVID-19 infections and mitigate the impact of the virus on Australians, including by acquiring and administering vaccines. </p>
<p>However, Australia also has <a href="https://www.etoconsortium.org/en/main-navigation/library/maastricht-principles/">obligations</a> to the people of other nations to facilitate access to vaccines for all. </p>
<p>These duties are not only about global humanism — there is also a strong global health argument to ensure everyone around the world is vaccinated. As GAVI, one of the organisations leading the global COVAX vaccine initiative, has reminded us, “<a href="https://www.gavi.org/vaccineswork/why-no-one-safe-until-everyone-safe-during-pandemic">no one is safe until everyone is safe</a>”. </p>
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<p>While large populations remain unvaccinated, variants of concern such as Delta will continue to evolve and may compromise global vaccine protection. Furthermore, global economic and social activity cannot return to anything like normal without extensive COVID-19 vaccination in all nations.</p>
<p>Global vaccine equity makes public health and economic sense for all countries, both rich and poor. Thus, Australia has an obligation — both to those in poorer countries <em>and to its own people</em> — to do what it reasonably can to increase vaccine access all over the world.</p>
<h2>Vaccine procurement and hoarding</h2>
<p>One of the main reasons for vaccine inequity is the shortage of vaccines. Access is a zero-sum game where one nation’s vaccine supply reduces the availability of doses for others.</p>
<p><a href="https://www.who.int/initiatives/act-accelerator/covax">The COVAX initiative</a> was established last year to enable global access to COVID-19 vaccines. COVAX’s role is to procure and allocate vaccines <a href="https://www.who.int/publications/m/item/allocation-mechanism-for-covax-facility-vaccines-explainer">with an aim of vaccinating</a> 20% of the people in participating countries by the end of 2021 — a <a href="https://www.abc.net.au/news/2021-06-22/most-poorer-countries-do-not-have-enough-covax-shots/100233082">target it is unlikely</a> to reach due to lack of supply. Once the 20% threshold is reached, COVAX intends to distribute its vaccines according to need.</p>
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<a href="https://theconversation.com/the-best-hope-for-fairly-distributing-covid-19-vaccines-globally-is-at-risk-of-failing-heres-how-to-save-it-158779">The best hope for fairly distributing COVID-19 vaccines globally is at risk of failing. Here's how to save it</a>
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<p>Despite COVAX, many nations have pursued their own procurement policies directly with vaccine manufacturers. In April, the <a href="https://digitallibrary.un.org/record/3921880?ln=en">UN Committee on Economic, Social and Cultural Rights</a> suggested such “vaccine nationalism” breached countries’ human rights obligations by undermining equitable access to vaccines.</p>
<p>However, the terms of the COVAX facility do not ban such bilateral deals. It is difficult, therefore, to maintain that it must dictate worldwide procurement.</p>
<p>But the hoarding of scarce vaccines does constitute a breach of countries’ obligations to protect global human rights. Indeed, the rights of a country’s own people are harmed by hoarding, as this perpetuates vaccine scarcity and delays the end of the global pandemic for everyone. </p>
<p>In this respect, it is wrong for rich countries to negotiate deals for vaccine booster shots before poorer countries have achieved significant vaccination rates. Tedros, the WHO chief, has <a href="https://www.abc.net.au/news/2021-07-13/who-tedros-covid-19-boosters-vaccine-inequality/100287792">rightly condemned</a> this.</p>
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<h2>Why AstraZeneca hesitancy has an impact beyond our borders</h2>
<p>Australia has <a href="https://www.health.gov.au/initiatives-and-programs/covid-19-vaccines/covid-19-vaccine-government-response/australias-vaccine-agreements#:%7E:text=The%20Government%20has%20made%20two,population%20to%20receive%202%20doses.">procured</a> enough AstraZeneca doses to vaccinate the entire country. In addition, we have advance-purchased enough Pfizer and Moderna doses to cover the entire population again, and enough Novavax to do so yet again. </p>
<p>The <a href="https://www.smh.com.au/national/nsw/premier-s-plea-consider-astrazeneca-if-you-are-under-40-20210722-p58c3f.html">only vaccine currently available in large amounts</a> in Australia is AstraZeneca because the local biotech company CSL <a href="https://www.smh.com.au/business/companies/csl-open-to-new-manufacturing-options-after-astrazeneca-production-20210504-p57om8.html">manufactures it</a>, and the government failed to prioritise its other deals last year.</p>
<p>The shifting official advice on AstraZeneca, however, has fuelled hesitancy in Australia, and has had an unintended impact on global vaccine supply, further disadvantaging those in poorer countries.</p>
<p>The AstraZeneca vaccine is safe and highly <a href="https://www.reuters.com/business/healthcare-pharmaceuticals/astrazeneca-covid-19-vaccine-effective-against-variants-found-india-2021-06-22/">effective</a>, bearing in mind that almost all medicines entail <a href="https://www.medicalnewstoday.com/articles/161255">risks</a>. However, under advice from the Australian Technical Advisory Group on Immunisation (<a href="https://www.health.gov.au/committees-and-groups/australian-technical-advisory-group-on-immunisation-atagi">ATAGI</a>), it is <a href="https://www.health.gov.au/news/atagi-statement-on-revised-recommendations-on-the-use-of-covid-19-vaccine-astrazeneca-17-june-2021">not the preferred vaccine for people under 60</a>. Most Australians, including many over 60, are now waiting for Pfizer. </p>
<p>That is not surprising given the ATAGI advice, and the messaging from the <a href="https://www.abc.net.au/news/2021-04-08/scott-morrison-announces-pfizer-preferred-for-younger-people/100057184">federal government</a> and <a href="https://www.abc.net.au/news/2021-06-30/qld-cho-rejects-morrisons-astrazeneca-comments-covid-vaccine/100256022">some state governments</a>, together with negative inputs from many <a href="https://www.theage.com.au/national/unqualified-and-dishonest-the-experts-who-undermined-confidence-in-astrazeneca-will-cost-australians-lives-20210722-p58c1f.html">medical professionals</a> and the <a href="https://www.smh.com.au/national/norman-swan-admits-i-probably-did-cause-some-vaccine-hesitancy-20210505-p57p82.html">media</a>. </p>
<p>This has induced an <a href="https://www.smh.com.au/national/worried-about-astrazeneca-me-too-the-way-we-think-about-risk-might-be-the-problem-20210720-p58beh.html">exaggerated perception of the risk of blood clots</a> caused by the vaccine. The reputation of the AstraZeneca vaccine has been wrongly and perhaps irreparably tarnished here.</p>
<p>The ATAGI advice has been influenced by Australia’s low COVID infection rate. And it has now <a href="https://www.health.gov.au/news/atagi-statement-response-to-nsw-covid-19-outbreak-24th-july-2021">changed its advice for all adults in NSW</a>, given the state’s large outbreak at the moment.</p>
<p>ATAGI has faithfully fulfilled its mandate of assessing risks on an individual basis, but that mandate is <a href="https://twitter.com/Pollytics/status/1417761636287324166?s=20">not entirely suitable</a> for a pandemic affecting all of society. The advice does not seem to account for the societal benefits for all — health, social and economic — of a more rapid vaccination rollout with an overwhelmingly safe and effective vaccine. </p>
<p>Unsurprisingly, ATAGI took no account of the impact of Australia’s AstraZeneca hesitancy on global vaccine access. Yet, Australia is now rapidly commandeering <a href="https://www.abc.net.au/news/2021-07-09/australia-to-get-pfizer-covid19-vaccine-supply-august/100279944">more Pfizer doses</a> as a result, which is pushing other nations further down the vaccine queue. And this is while we eschew our plentiful AstraZeneca supplies.</p>
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<h2>Addressing the zero-sum game</h2>
<p>Beyond issues regarding the sharing of vaccines, a bigger imperative is to address the root of the problem: <a href="https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3876848">vaccine scarcity</a>. All nations, including Australia, must do what they can to increase the production of vaccines so the supply can more swiftly meet the demand.</p>
<p>Hence, those countries with vaccine manufacturing capacity must utilise it more effectively. For example, Australia must ensure CSL continues to manufacture as much AstraZeneca as it can, at least until it switches production to another vaccine (possibly <a href="https://www.smh.com.au/business/companies/we-do-not-have-capacity-to-make-the-novavax-vaccine-says-csl-20210114-p56u1a.html">Novavax</a>). </p>
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Read more:
<a href="https://theconversation.com/over-700-health-experts-are-calling-for-urgent-action-to-expand-global-production-of-covid-vaccines-159701">Over 700 health experts are calling for urgent action to expand global production of COVID vaccines</a>
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<p>We are concerned over reports <a href="https://www.theguardian.com/australia-news/2021/jul/16/australian-production-of-astrazeneca-vaccine-in-early-july-just-one-tenth-what-government-promised">CSL has slowed its AstraZeneca manufactureing</a>, though hopefully this is only temporary. </p>
<p>It is a major public policy failure that AstraZeneca has been perceived as “not good enough” for Australians. If we won’t take it, we must donate it to save lives elsewhere, especially while we queue-jump for more Pfizer doses.</p>
<p>Australia has human rights obligations to greatly enhance its support for global vaccine equity. Failure to do so not only harms global health, but also the reputation and safety of our country.</p><img src="https://counter.theconversation.com/content/165001/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>If Australians won’t take the AstraZeneca vaccine, we must donate it to save lives elsewhere, especially while we queue-jump for more Pfizer doses.Sarah Joseph, Professor of Human Rights Law, Griffith UniversityGregory Dore, Infectious Diseases Physician, St Vincent's Hospital, Sydney; Scientia Professor, Kirby Institute, UNSW SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1573992021-03-18T04:32:35Z2021-03-18T04:32:35ZAs Australia’s COVID vaccine rollout splutters, we need transparency about when international borders might reopen<p>The Australian government’s offer of <a href="https://www.abc.net.au/news/2021-03-10/tourism-coronavirus-pandemic-assistance-package-cheap-flights/13235432">half-price airfares to encourage domestic tourism</a> highlights another item of unfinished COVID policy business: when will Australia’s international borders be reopened?</p>
<p>The border questions, such as when to remove <a href="https://www.smartraveller.gov.au/COVID-19/leaving-Australia">exit controls</a> and lift hotel quarantine for arrivals, have profound implications for the economy.</p>
<p>Border closures have been key to Australia escaping the worst ravages of the pandemic and successfully pursuing an elimination strategy on COVID-19.</p>
<p>Widespread vaccinations will eventually enable Australia to reopen its borders. The question is when.</p>
<p>The federal government should be explicit about what proportion of the population it judges will need to be vaccinated to warrant border reopening. Australians could then measure progress towards that goal. </p>
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<h2>The vaccination program is off to a slow start</h2>
<p>Australia’s vaccine program has been much-trumpeted, but troubled. Key elements of a successful mass vaccination program have not been in place including:</p>
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<li><p>mass vaccination <a href="https://www.england.nhs.uk/coronavirus/publication/vaccination-sites/">venues</a></p></li>
<li><p>a booking and prioritisation system that works and <a href="https://www.omnicalculator.com/health/vaccine-queue-uk?fbclid=IwAR3Mhv3t7l4ARHXv0ea9kpuClHAjVL1MjZ4H5L2ajQm48xlXbeAgOtKXthk">lets people know within a 3-4 week window when their turn might be</a>, as the United Kingdom’s does</p></li>
<li><p>a logistical system that gets vaccines to the right place at the right time and enables tracking of deliveries by recipients. I’ve heard from several GPs that they <a href="https://www.abc.net.au/news/2021-03-17/covid-gp-clinics-vaccine-rollout-confusion/13255874">don’t know how many vaccines they’re going to get and when</a>.</p></li>
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<p>Federal Health Minister Greg Hunt’s announcement today of <a href="https://www.abc.net.au/news/2021-03-18/coronavirus-australia-live-updates-covid19-latest-news-vaccine/100015526">more than 100 new vaccination clinics</a> is a step in the right direction, but it alone isn’t enough to fix the botched rollout. </p>
<p>No deadlines for the rollout have yet been met, and the target end date <a href="https://theconversation.com/australias-covid-vaccine-rollout-is-well-behind-schedule-but-dont-panic-157048">appears to have already slipped</a>, from October 2021 to <a href="https://www.smh.com.au/politics/federal/not-all-second-covid-19-shots-will-be-delivered-by-october-20210311-p579tv.html">January 2022</a>.</p>
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Read more:
<a href="https://theconversation.com/australias-covid-vaccine-rollout-is-well-behind-schedule-but-dont-panic-157048">Australia's COVID vaccine rollout is well behind schedule — but don't panic</a>
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<p>The rollout for the first groups (phase 1A), including <a href="https://www.health.gov.au/initiatives-and-programs/covid-19-vaccines/getting-vaccinated-for-covid-19/when-will-i-get-a-covid-19-vaccine">quarantine and front-line health workers and aged-care residents</a>, has proceeded slowly.</p>
<p>So far, it appears that low vaccination rates are not primarily due to problems of overseas supply as only a fraction of the <a href="https://www.smh.com.au/politics/federal/100-000-australians-vaccinated-as-more-covid-19-vaccine-doses-arrive-20210310-p579bf.html">doses that have arrived from overseas</a> <a href="https://www.health.gov.au/initiatives-and-programs/covid-19-vaccines/getting-vaccinated-for-covid-19#australias-vaccine-rollout">have been used</a>.</p>
<p>The second stage of the rollout (phase 1B) started badly, with a <a href="https://www.theguardian.com/australia-news/2021/mar/18/what-the-hell-industry-sources-say-government-rushed-launch-of-covid-vaccine-booking-system">botched booking system</a> leading to GPs being overwhelmed by callers but with practices having no idea when they would get vaccines nor how many.</p>
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<p>The vaccination rollout involved what Greg Hunt described as “<a href="https://www.9news.com.au/health/coronavirus-australia-vaccine-rollout-massive-logistical-operation-greg-hunt/05d4758d-ca0d-4fdd-8567-3a513fa239b5">one of the largest logistical exercises in Australia’s history</a>”. Unfortunately, it hasn’t gone smoothly so far, with <a href="https://www.theguardian.com/australia-news/2021/feb/26/australias-covid-vaccine-rollout-errors-cancellations-and-missed-deadlines">inadequate notice, messed-up deliveries and cancellations</a>.</p>
<p>Australia will be less reliant on international supplies from March 22, when domestically produced vaccines will begin <a href="https://www.abc.net.au/news/2021-03-05/astrazeneca-vaccine-australian-made-rollout-from-march-22/13220254">rolling off the CSL production line</a>.</p>
<h2>What’s the target?</h2>
<p>Once the teething problems are fixed, the federal government should tell us what proportion of the population will need to be fully vaccinated before it reopens the external borders.</p>
<p>Once borders are reopened and hotel quarantine is no longer universally required, the risk of COVID infection will increase. Australians’ principal protection against that risk will be through vaccine-derived herd immunity. <a href="https://jamanetwork.com/journals/jama/article-abstract/2777391">Assuming</a> the <a href="https://www.medrxiv.org/content/10.1101/2021.02.25.21252415v1">vaccine protects against transmission</a>, fewer people will get infected because there will be fewer unprotected people.</p>
<p>The level of vaccination required to achieve herd immunity is affected by <a href="https://arxiv.org/pdf/2103.07061.pdf">how infectious the virus is</a>, and this is changing with new variants. But it’s estimated we’ll need to vaccinate between <a href="https://www.nature.com/articles/s41577-020-00451-5?fbclid=IwAR1XjD0YOvTNAXN5Lw4VureGOzzxGfvXRwx4lpoxUaMysAq_4b_D51l0gUw">65%</a> and <a href="https://www.thelancet.com/article/S0140-6736(20)32318-7/fulltext">90%</a> of the whole population. If the necessary figure proves to be at the high end of that range, Australia may never achieve herd immunity, given the extent of vaccine hesitancy and the reality that the <a href="https://www.tga.gov.au/apm-summary/comirnaty">Pfizer vaccine has only been approved for people aged 16 and over</a> and <a href="https://www.tga.gov.au/apm-summary/covid-19-vaccine-astrazeneca">AstraZeneca for people 18 and over</a>.</p>
<p>According to various surveys, somewhere between <a href="https://pursuit.unimelb.edu.au/articles/more-australians-becoming-wary-of-covid-19-vaccines">15%</a> and <a href="https://www.theguardian.com/australia-news/2021/feb/16/two-thirds-of-australians-definitely-want-covid-vaccine-while-27-are-unsure">30%</a> are hesitant about getting the vaccine, with possibly up to <a href="https://pursuit.unimelb.edu.au/articles/more-australians-becoming-wary-of-covid-19-vaccines">20% potentially refusing the vaccine</a>. </p>
<p>But it’s not a new phenomenon and there are <a href="https://www.sciencedirect.com/science/article/pii/S0264410X15005046">ways to increase vaccine uptake</a>. For example, if uptake isn’t reaching the necessary levels, airlines or governments could mandate <a href="https://www.qantasnewsroom.com.au/qantas-responds/qantas-group-position-on-covid-19-vaccination-for-international-travel/">proof of vaccination for air travel</a>. Or, as proposed in the United States, governments could <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/fully-vaccinated.html">relax restrictions on masks or gatherings for vaccinated people</a>. In that context, the government could consider restricting its half-price airlines package to people who have been vaccinated.</p>
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<p>The threshold for herd immunity is a scientific question, and the answer may not be known for many months. But the important question remains: given what we know about the virus today, what level of vaccination means the risks to people and the economy of opening borders is commensurate with the benefits?</p>
<p>This is a question for national cabinet, or if consensus cannot be achieved there, for the federal government. The government has <a href="https://onlinelibrary.wiley.com/doi/full/10.1111/puar.13224">constitutional power over quarantine</a>. Federal responsibilities also include international trade, including tourism and international students, and the fate of Australians stranded overseas.</p>
<h2>And if we achieve herd immunity?</h2>
<p>Once the threshold of herd immunity is achieved, states can abandon their trigger-happy use of lockdowns, and rely more on traditional public health approaches to infection control. These include ensuring their testing, tracing and isolation systems are up to scratch. Each state should learn from the best aspects of other states’ systems.</p>
<p>The federal government is in charge of vaccinating the general community, but it should invite the states to assist so they contribute more to the national vaccination effort. The states could help overcome the backlog, speed up the vaccination rate and help establish mass vaccination centres.</p>
<p>Reopening the external borders will be a key step along the path back to something approaching normality. The federal government should specify the criteria for reopening, to give Australians some certainty about what their travel future will look like.</p><img src="https://counter.theconversation.com/content/157399/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Grattan Institute began with contributions to its endowment of $15 million from each of the Federal and Victorian Governments, $4 million from BHP Billiton, and $1 million from NAB. In order to safeguard its independence, Grattan Institute’s board controls this endowment. The funds are invested and contribute to funding Grattan Institute's activities. Grattan Institute also receives funding from corporates, foundations, and individuals to support its general activities, as disclosed on its website.</span></em></p>The government should be explicit about what proportion of the population will need to be vaccinated to warrant border reopening. Australians could then measure progress towards that goal.Stephen Duckett, Director, Health Program, Grattan InstituteLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1519112020-12-11T01:53:42Z2020-12-11T01:53:42ZHow did the University of Queensland/CSL vaccine fail due to ‘false positive’ HIV tests? A vaccine expert explains<p>Australia’s hopes of a locally developed COVID-19 vaccine have been dashed with <a href="https://www.abc.net.au/news/2020-12-11/uq-csl-coronavirus-vaccine-trial-to-be-abandoned/12973656">news today</a> the University of Queensland/CSL vaccine would not proceed to further clinical trials.</p>
<p>Unlike news about the <a href="https://theconversation.com/people-with-severe-allergies-warned-off-pfizer-covid-vaccine-for-now-but-that-may-change-as-more-details-emerge-151837">Pfizer/BioNTech COVID vaccine</a> earlier this week, there were no safety concerns with the UQ/CSL vaccine.</p>
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<p>According to a <a href="https://cdn.theconversation.com/static_files/files/1373/CSL_ASX_statement.pdf?1607639828">statement</a> to the Australian Stock Exchange (ASX) earlier today, CSL said participants in the phase 1 trial received “false positive” results to HIV tests. They were not infected with HIV, nor did the vaccine contain the entire HIV virus.</p>
<p>Rather, the vaccine’s signature “molecular clamp” technology was formulated with parts of <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672035/">an HIV protein</a>. When injected, these prompted the production of antibodies that were picked up in a range of HIV tests. In other words, if the vaccine had been widely rolled out, this could lead many people to think they had HIV when they didn’t.</p>
<p>The news prompted the federal government to announce <a href="https://www.bloomberg.com/news/articles/2020-12-10/australia-cancels-order-for-csl-vaccine-as-trial-stumbles">it had cancelled</a> its agreement to supply the UQ/CSL vaccine, which was always contingent on successfully completing clinical trials. </p>
<p>Instead, the government will supply more doses of other vaccines, including 20 million extra doses of the University of Oxford/AstraZeneca vaccine, to be made by CSL.</p>
<p>The Oxford/AstraZeneca COVID vaccine is the first with <a href="https://theconversation.com/the-oxford-astrazeneca-vaccine-is-the-first-to-publish-peer-reviewed-efficacy-results-heres-what-they-tell-us-and-what-they-dont-151755">published peer-reviewed results</a> from phase 3 clinical trials, a significant milestone. </p>
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<a href="https://theconversation.com/the-oxford-astrazeneca-vaccine-is-the-first-to-publish-peer-reviewed-efficacy-results-heres-what-they-tell-us-and-what-they-dont-151755">The Oxford/AstraZeneca vaccine is the first to publish peer-reviewed efficacy results. Here's what they tell us — and what they don't</a>
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<p>As well as the Oxford/AstraZeneca vaccine, existing arrangements are in place to supply Australians with the Pfizer/BioNTech and Novavax vaccines, should they prove safe and effective. That’s as well as vaccines available under the World Health Organisation-backed <a href="https://theconversation.com/australias-just-signed-up-for-a-shot-at-9-covid-19-vaccines-heres-what-to-expect-146750">COVAX agreement</a>.</p>
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Read more:
<a href="https://theconversation.com/australias-just-signed-up-for-a-shot-at-9-covid-19-vaccines-heres-what-to-expect-146750">Australia's just signed up for a shot at 9 COVID-19 vaccines. Here's what to expect</a>
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<h2>How could a COVID vaccine lead to a positive HIV test?</h2>
<p>The UQ/CSL vaccine uses “<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672035/">molecular clamp</a>” technology to stop the coronavirus spike protein from “wobbling about”. This more stable presentation is more likely to lead to a protective immune response.</p>
<p>The molecular clamp in UQ’s vaccine contains part of an HIV protein, a string of 80 amino acids. By itself, this is harmless and cannot cause an HIV infection or AIDS.</p>
<p>But there was always a theoretical possibility that once injected as part of the vaccine formulation, people’s immune systems would recognise it as “foreign” and raise antibodies against it. Until now, the research team thought the chance of that happening was low. And in its ASX statement CSL said people in the 216-person trial were fully informed of this possibility.</p>
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<p>However, from what we’ve heard today, it’s clear that people’s immune systems did recognise the HIV protein fragment in the molecular clamp.</p>
<p>Had we rolled out this vaccine on a wider scale, we would have seen many more “false positive” HIV tests. This would have meant unnecessary anxiety while people sought further clarification about their HIV status.</p>
<p>It would also have undermined the public’s confidence in the COVID vaccination program. You have to have the public on board. So by acting early to clearly communicate concerns, the researchers have acted appropriately. And this should reinforce the public’s confidence in Australia’s COVID vaccination program, due to start from March 2021.</p>
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Read more:
<a href="https://theconversation.com/what-will-australias-covid-vaccination-program-look-like-4-key-questions-answered-150748">What will Australia's COVID vaccination program look like? 4 key questions answered</a>
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<h2>Is this the end of UQ’s ‘molecular clamp’ technology?</h2>
<p>This particular molecular clamp is unique to UQ. So while this particular type will not be used for future vaccines, it’s likely the researchers will investigate and modify it to reduce the chance of any further HIV cross-reactivity.</p>
<p>I certainly don’t think it’s the end of this technology.</p>
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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>So where does this leave us?</h2>
<p>We’ve known all along that not all COVID-19 vaccines in early clinical trials would be successful. Safety issues or a lack of protection will halt some. But in this case, we had something different — a complication that would lead people to believe they had HIV when they didn’t, undermining people’s confidence in the COVID vaccine program.</p>
<p>That’s why it’s still important to pursue a broad portfolio of vaccine approaches and technologies. We don’t want to put all our eggs in one basket.</p>
<p>It’s also important to remember that even though the UQ/CSL vaccine will not proceed to late-stage clinical trials, phase 1 trials will continue, with results submitted for peer review in due course. That means researchers can analyse the results in more detail.</p><img src="https://counter.theconversation.com/content/151911/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Adam Taylor receives funding from the National Health and Medical Research Council of Australia and the National Foundation for Medical Research and Innovation with the New South Wales Department of Primary Industries. </span></em></p>If the vaccine had been widely rolled out, people would think they had HIV when they didn’t. But it’s not the end of this type of technology.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/1489962020-11-03T19:08:02Z2020-11-03T19:08:02ZAustralia may miss out on several COVID vaccines if it can’t make mRNA ones locally<p>The Australian government is in talks with pharmaceutical company Pfizer about potentially supplying <a href="https://www.canberratimes.com.au/story/6985523/government-in-more-vaccine-talks-under-pressure-to-release-more-detail/">its COVID-19 vaccine</a>. The company has also secured preliminary clearance to apply for a type of <a href="https://www.tga.gov.au/tga-grants-second-provisional-determination-covid-19-vaccine">fast-tracked regulatory approval</a> for this vaccine.</p>
<p>But even if clinical trials showed this vaccine was safe and effective, Australia couldn’t make enough doses. We just don’t have the manufacturing capacity or technology in place.</p>
<p>So, has Australia missed a trick in not tooling up for these mRNA vaccines?</p>
<h2>What are mRNA vaccines?</h2>
<p>mRNA vaccines are coated molecules of mRNA, similar to DNA, that carry the instructions for making a viral protein. </p>
<p>After injection into muscle, the mRNA is taken up by cells. Ribosomes, the cell’s protein factories, read the mRNA instructions and make the viral protein. These new proteins are exported from cells and the rest of the immunisation process is identical to other vaccines: our immune system mounts a response by recognising the proteins as foreign and developing antibodies against them. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/367151/original/file-20201103-17-q4gg0k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Infographic showing how mRNA vaccines work" src="https://images.theconversation.com/files/367151/original/file-20201103-17-q4gg0k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/367151/original/file-20201103-17-q4gg0k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=298&fit=crop&dpr=1 600w, https://images.theconversation.com/files/367151/original/file-20201103-17-q4gg0k.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=298&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/367151/original/file-20201103-17-q4gg0k.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=298&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/367151/original/file-20201103-17-q4gg0k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=375&fit=crop&dpr=1 754w, https://images.theconversation.com/files/367151/original/file-20201103-17-q4gg0k.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=375&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/367151/original/file-20201103-17-q4gg0k.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=375&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">mRNA vaccines work by delivering instructions to cells to make viral proteins. The body then makes these proteins, and the immune system recognises them and mounts an immune response.</span>
<span class="attribution"><span class="source">Created with BioRender.com</span>, <span class="license">Author provided</span></span>
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<p>mRNA vaccines have several advantages. Their production process is almost identical for any possible mRNA. This means mRNA vaccines can be rapidly designed for new viruses or strains. This speed of design is why the COVID-19 mRNA vaccines are current frontrunners, and will probably be the first to get <a href="https://www.pfizer.com/news/hot-topics/an_open_letter_from_pfizer_chairman_and_ceo_albert_bourla">approval</a> by the US Food and Drug Administration. </p>
<p>mRNA vaccines can be <a href="https://www.frontiersin.org/articles/10.3389/fimmu.2020.583077/full">potentially quicker and cleaner to make</a> than other vaccines. Unlike other types of vaccines made in living cells such as chicken eggs or genetically modified cell cultures, mRNA molecules can be made in an apparatus called a bioreactor. Some mRNA vaccines, such as Imperial College London’s vaccine now <a href="https://www.clinicaltrialsarena.com/news/imperial-college-covid-vaccine/">undergoing testing</a>, are even self-replicating. This means the mRNA can copy itself inside our cells, so protein production lasts longer and, potentially, fewer doses are needed.</p>
<p>However, mRNA vaccines also have some disadvantages. As a new technology, no mRNA vaccine has ever been approved for clinical use. Unlike other vaccines, we do not have years of data on the safety of this type of vaccine to reassure the public.</p>
<p>They also need to be stored at very low temperatures. For example, Moderna’s needs to be kept at -20°C and Pfizer’s at -70°C. At normal refrigerator temperatures of 2-8°C, they tend to last just a day or two. This means distribution may be difficult, especially in the developing world.</p>
<p>And crucially, most countries — including Australia — don’t have the mRNA manufacturing capability needed to make these vaccines at the required scale. So while the production of mRNA is cleaner, it may also be slowed by supply chain issues. </p>
<h2>Which mRNA vaccines are the frontrunners?</h2>
<p>There are six mRNA COVID-19 vaccines in clinical trials: </p>
<ul>
<li><p>mRNA-1273 (Moderna, US) and BNT162 (Pfizer/BioNTech, Germany), both in phase 3 trials</p></li>
<li><p>CvnCoV (CureVac, Germany), phase 2</p></li>
<li><p>LUNAR-COV19 (Arcturus/Duke-NUS, Singapore), phase 1-2</p></li>
<li><p>COVAC1 (Imperial College, UK) and Covidvax (People’s Liberation Army Academy of Military Sciences/Walvax Biotech, China), both in phase 1. </p></li>
</ul>
<p>The Moderna and CureVac candidates are both part of the <a href="https://theconversation.com/australias-just-signed-up-for-a-shot-at-9-covid-19-vaccines-heres-what-to-expect-146750">COVAX initiative</a>, a World Health Organisation-sponsored drive to boost vaccine research and give member countries a wider range of potential candidates.</p>
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Read more:
<a href="https://theconversation.com/australias-just-signed-up-for-a-shot-at-9-covid-19-vaccines-heres-what-to-expect-146750">Australia's just signed up for a shot at 9 COVID-19 vaccines. Here's what to expect</a>
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<p>As a COVAX member, Australia will have access to buy and distribute either of these vaccines if successful in clinical trials, and could also license the technology to make the vaccines domestically.</p>
<p>But Australia does not currently have the capacity to manufacture clinical-grade mRNA vaccines. Melbourne-headquartered global biotech firm CSL <a href="https://www.csl.com/news/2020/20200907-csl-to-manufacture-and-supply-uq-and-ou-vaccine-candidates-for-australia">can make</a> protein-based vaccines, and has expanded its capacity to include DNA/viral vaccines, but not mRNA. </p>
<p>CSIRO has facilities for making <a href="https://www.csiro.au/en/Research/MF/Areas/Biomedical/cGMP">clinical-grade proteins</a> for phase 1 and 2 clinical trials, but not vaccine-grade mRNA, and not at the scale needed for clinical trials, let alone for immunising the entire population.</p>
<h2>Concerns raised</h2>
<p>Australian scientists recently <a href="https://www.afr.com/companies/healthcare-and-fitness/manufacturing-is-the-missing-link-in-vaccine-supply-chain-20200709-p55alx">raised concerns</a> about the lack of capacity for mRNA vaccine production.</p>
<p>In August, federal science and technology minister Karen Andrews, <a href="https://www.minister.industry.gov.au/ministers/karenandrews/media-releases/submissions-sought-covid-19-vaccine-and-treatment-production">called</a> on Australian businesses to come forward if they can help with vaccine production and distribution.</p>
<p>It is not publicly known whether any company responded indicating it could make mRNA vaccines. </p>
<p>With the federal government prepared to invest A$330 million in research for COVID vaccines and treatment, and mRNA vaccines <a href="https://www.fool.com/investing/2020/10/14/here-are-the-only-2-coronavirus-vaccines-that-coul/">clearly leading the global race</a>, it’s possible some Australian biotech firms could pivot to mRNA production.</p>
<p>The CSL global product pipeline includes <a href="https://www.csl.com/research-and-development/product-pipeline">an mRNA vaccine against the flu</a> in pre-clinical development. But CSL has issued no public statement about its capacity for Australian production of clinical-grade mRNA vaccines if this, or one of the COVID-19 mRNA candidate vaccines, requires a local supply. CSL has not declared any desire to establish mRNA manufacturing in Australia at this time.</p>
<h2>So what should Australia do?</h2>
<p>Australia’s first option will be to buy doses from overseas. But despite the COVAX deal it may still be at the end of a long queue, given the hundreds of millions of doses of Pfizer mRNA vaccine <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-announce-agreement-us-government-600">already pre-purchased by the United States</a>, <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-supply-japan-120-million-doses-their">Japan</a> and <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-potentially-supply-eu-200-million-doses">the European Union</a>, and similar deals for these and other countries in negotiation with Moderna.</p>
<p>Compare this with Germany, where a <a href="https://www.businessinsider.com.au/moderna-biontech-stock-price-covid19-vaccine-update-deal-with-takeda-2020-10?r=US&IR=T">planned rollout</a> of the Pfizer vaccine to the elderly will start 24 hours after emergency approval, potentially as early as this month.</p>
<p>With the dose <a href="https://www.cnbc.com/2020/08/05/moderna-is-pricing-coronavirus-vaccine-at-32-to-37-per-dose-for-some-customers.html">costing US$20-40 per person</a>, even if we can secure doses, it could cost up to A$1 billion to immunise the Australian population if we buy the vaccine.</p>
<p>The second option is to to set up production of mRNA vaccines here, potentially led by a biotech firm with approval to make clinical-grade therapeutics. As a rough estimate, we calculate it could cost as little as A$100 million to make sufficient vaccine domestically. But it will mean a significant lag time, perhaps 12 months, to set up the infrastructure and train staff.</p>
<p>The lack of capacity to make mRNA is both a threat and an opportunity for the Australian biotechnology sector. Given the speed at which this technology has been applied to COVID-19, it would be useful to have this production capacity in Australia, so we can quickly respond to future pandemics.</p>
<p>Beyond vaccines, mRNA could be used for <a href="https://www.nature.com/articles/d41586-019-03074-6">other promising therapies</a> for cancer and other genetic diseases.</p>
<p>There is also the opportunity for creative innovation in this area. Tesla <a href="https://www.sec.gov/Archives/edgar/data/1809122/000110465920095636/tm2016252-23_424b4.htm">used its robotics capacity</a> to create an mRNA synthesis platform for German biotech firm CureVac.</p>
<p>With investment by the federal government and willingness from the private sector, Australia could be part of this innovation wave. This technology would be useful for COVID-19 mRNA vaccines, future pandemics, and future medicines more broadly.</p>
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<p><em>The author thanks the following researchers for contributions that helped inform this article: Damian Purcell, Peter Doherty Institute, University of Melbourne; Colin Pouton, Monash Institute of Pharmaceutical Sciences; Thomas Preiss, John Curtin School of Medical Research, ANU; Pall Thordarson, UNSW; and Nigel McMillan, Griffith University.</em></p><img src="https://counter.theconversation.com/content/148996/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Archa Fox is Associate Professor at the University of Western Australia and a Future Fellow of the Australian Research Council. She receives funding from the Australian Research Council and the National Health and Medical Research Council. She is a director of the International RNA Society and president of the RNA Network of Australia</span></em></p>So-called mRNA vaccines are among the frontrunners in the global race to design a COVID vaccine. But as a new technology, most nations, including Australia, lack the capacity to produce them at scale.Archa Fox, Associate Professor and ARC Future Fellow, The University of Western AustraliaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1456932020-09-08T05:16:11Z2020-09-08T05:16:11ZPutting our money on two COVID vaccines is better than one: why Australia’s latest vaccine deal makes sense<figure><img src="https://images.theconversation.com/files/356857/original/file-20200908-16-1h66go4.jpg?ixlib=rb-1.1.0&rect=9%2C0%2C6029%2C4010&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>Yesterday, <a href="https://www.pm.gov.au/media/australia-secures-onshore-manufacturing-agreements-two-covid-19-vaccines">Prime Minister Scott Morrison</a> announced Australians will get access to 84.8 million COVID-19 vaccine doses throughout 2021, provided current trials prove the vaccines in question are safe and effective.</p>
<p>A series of deals worth A$1.7 billion between the federal government and two major pharmaceutical companies would see the local production and supply of two vaccines, developed by the University of Oxford and the University of Queensland, respectively.</p>
<p>So what’s in the deals, what are the vaccines, and are we picking the best of the bunch for a fair price?</p>
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<h2>What’s the deal?</h2>
<p>The current and <a href="https://theconversation.com/the-oxford-deal-is-welcome-but-remember-the-vaccine-hasnt-been-proven-to-work-yet-144726">previous deals</a> represent progress in negotiations between the Australian government, UK/Sweden-based pharmaceutical company AstraZeneca, and Melbourne-based biotechnology company CSL. The ultimate aim is a formal agreement to manufacture the two vaccines in Australia.</p>
<p>Previously, the government signed a <a href="https://www.astrazeneca.com.au/media/press-releases/2020/australia-and-new-zealand-covid-19-response.html">letter of intent</a> with AstraZeneca, which is working with University of Oxford researchers to test their AZD1222 vaccine. </p>
<p>But AstraZeneca needed a manufacturer in Australia to make the vaccine locally. The biggest local vaccine manufacturer is CSL, which is also working with the University of Queensland to test its V451 vaccine.</p>
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Read more:
<a href="https://theconversation.com/the-oxford-deal-is-welcome-but-remember-the-vaccine-hasnt-been-proven-to-work-yet-144726">The Oxford deal is welcome, but remember the vaccine hasn't been proven to work yet</a>
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<p>The <a href="https://www.csl.com/news/2020/20200907-csl-to-manufacture-and-supply-uq-and-ou-vaccine-candidates-for-australia">latest developments</a> include two “<a href="https://www.investopedia.com/terms/h/headsofagreement.asp">heads of agreement</a>” — non-binding documents that outline the basic terms of a tentative deal:</p>
<ul>
<li><p>CSL and AstraZeneca agreed CSL will produce and supply 30 million doses of AZD1222, from early 2021</p></li>
<li><p>CSL and the government agreed CSL will produce and supply 51 million doses of V451, from mid-2021.</p></li>
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<p>The government and CSL also entered a <a href="https://www.csl.com/news/2020/20200907-csl-to-manufacture-and-supply-uq-and-ou-vaccine-candidates-for-australia">funding deed</a> worth up to A$1.7 billion, under which CSL will prepare to manufacture AZD1222 and one other COVID-19 vaccine (likely V451). </p>
<p>Meanwhile, the government and AstraZeneca have a separate agreement to supply 3.8 million doses produced overseas in early 2021 for vulnerable people and health-care workers.</p>
<p>The final formal agreement remains contingent on whether the vaccines protect against COVID-19 in clinical trials currently underway.</p>
<h2>A recap of the vaccines</h2>
<p>Oxford and AstraZeneca have what’s called a viral vector vaccine. Researchers take a fairly harmless virus (in this case an <a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0040385">adenovirus from chimpanzees</a>) and modify it to produce a target (here they’ve used the spike protein of SARS-CoV-2, the coronavirus that causes COVID-19).</p>
<p>A viral vector looks like a virus to our immune system, so the idea is it can train our body to mount a strong response against SARS-CoV-2. But the viral vector can’t cause disease.</p>
<figure class="align-center ">
<img alt="An illustration of SARS-CoV-2, the coronavirus that causes COVID-19." src="https://images.theconversation.com/files/356860/original/file-20200908-20-9fato9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/356860/original/file-20200908-20-9fato9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/356860/original/file-20200908-20-9fato9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/356860/original/file-20200908-20-9fato9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/356860/original/file-20200908-20-9fato9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/356860/original/file-20200908-20-9fato9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/356860/original/file-20200908-20-9fato9.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">The spike protein, on the surface of the SARS-CoV-2 virus, has been important in developing a vaccine.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
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<p>The University of Queensland and CSL have a protein subunit vaccine, which also uses the spike protein as a target. Unfortunately, spike protein is notorious for changing its shape, which makes it harder for our immune system to recognise. </p>
<p>So the University of Queensland has developed a <a href="https://www.uq.edu.au/news/article/2020/01/race-develop-coronavirus-vaccine">molecular clamp</a> to hold the spike protein in the correct shape. The clamped spike is then mixed with an adjuvant, a compound that stimulates an immune response. The adjuvant here is MF59, used in some <a href="https://www.cdc.gov/flu/prevent/adjuvant.htm">influenza vaccines for older people</a>.</p>
<p>AstraZeneca has started <a href="https://www.nih.gov/news-events/news-releases/phase-3-clinical-testing-us-astrazeneca-covid-19-vaccine-candidate-begins">vaccinating volunteers</a> as part of phase 3 clinical trials in the United States, while CSL and the University of Queensland are <a href="https://stories.uq.edu.au/news/2020/first-human-trial-of-UQs-COVID-19-vaccine/index.html">vaccinating volunteers</a> for their phase 1 clinical trial in Australia.</p>
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Read more:
<a href="https://theconversation.com/5-ways-we-can-prepare-the-public-to-accept-a-covid-19-vaccine-saying-it-will-be-mandatory-isnt-one-144730">5 ways we can prepare the public to accept a COVID-19 vaccine (saying it will be 'mandatory' isn't one)</a>
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</em>
</p>
<hr>
<h2>Two promising candidates</h2>
<p>Until a vaccine is shown to work in a phase 3 clinical trial, it’s educated guesswork as to which will be effective.</p>
<p>Selecting two very different types of vaccines is a good strategy though. Each has different pros and cons, and we’ll have a better chance of ending up with an effective vaccine, than, say, if we were banking on two similar candidates.</p>
<p>The Oxford/AstraZeneca vaccine can be made quickly and should generate immunity <a href="https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0006870">after a single shot</a>. Only <a href="https://www.fda.gov/news-events/press-announcements/first-fda-approved-vaccine-prevention-ebola-virus-disease-marking-critical-milestone-public-health">one viral vector vaccine</a> has been approved before, for Ebola, so it’s more experimental. But it’s already well advanced through clinical trials.</p>
<p>The Queensland/CSL vaccine takes longer to make as manufacturing large amounts of protein can be difficult, and it will <a href="https://clinicaltrials.gov/ct2/show/NCT04495933?term=University+of+Queensland&cond=COVID&draw=2&rank=3">require two shots</a>. But protein subunit vaccines are more of a known entity, routinely used to prevent <a href="https://www.cdc.gov/flu/prevent/qa_flublok-vaccine.htm">influenza</a> and <a href="https://immunisationhandbook.health.gov.au/vaccines/engerix-b">hepatitis B</a>.</p>
<h2>Why so many doses?</h2>
<p>Some 84.8 million doses may seem like a lot to vaccinate 25 million Australians. But it’s reasonable for two reasons.</p>
<p>First, each person might need two doses of vaccine to generate optimal immunity. For the Queensland/CSL vaccine, the pledged 51 million doses will allow for that and more.</p>
<p>A total of 33.8 million doses of the Oxford/AstraZeneca vaccine would allow for each person to get one, <a href="https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0006870">as intended</a> for this type of vaccine, with plenty to spare. But we should note <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31604-4/fulltext">early clinical trial data</a> has suggested two doses are better than one.</p>
<figure class="align-center ">
<img alt="A doctor's gloved hand disinfects the skin of a patient's upper arm in preparation for a vaccination." src="https://images.theconversation.com/files/356861/original/file-20200908-20-58fvbc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/356861/original/file-20200908-20-58fvbc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/356861/original/file-20200908-20-58fvbc.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/356861/original/file-20200908-20-58fvbc.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/356861/original/file-20200908-20-58fvbc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=501&fit=crop&dpr=1 754w, https://images.theconversation.com/files/356861/original/file-20200908-20-58fvbc.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=501&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/356861/original/file-20200908-20-58fvbc.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=501&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">We’ll need more doses of a COVID-19 vaccine than there are people in Australia.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<p>Second, it’s logistically challenging to get a vaccine from the manufacturer into a person’s arm. Not every dose will get to where it needs to go safely and on time. So we’ll need a few million extra doses, just in case.</p>
<h2>Is the price reasonable?</h2>
<p>There’s a <a href="https://www.fiercepharma.com/vaccines/china-sinopharm-chief-narrows-down-covid-19-vaccine-price-to-within-145-for-2-dose-regimen">large range</a> in pricing of potential COVID-19 vaccines. Some bulk deals are as low as roughly A$5.50 per dose (AstraZeneca) and other vaccines could be as high as around A$100 per dose (Sinopharm).</p>
<p>Several factors contribute to this variation, including differing manufacturing costs and profit margins.</p>
<p>The current deals with CSL average A$21 per dose, which is mid-range and reasonable considering the resources CSL will need to put towards reconfiguring their operations.</p>
<p>All in all, it’s a fair deal.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/vaccine-progress-report-the-projects-bidding-to-win-the-race-for-a-covid-19-vaccine-141412">Vaccine progress report: the projects bidding to win the race for a COVID-19 vaccine</a>
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</em>
</p>
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<h2>What happens next?</h2>
<p>All eyes will be on the phase 3 trial results for AZD1222, expected in October. If these are good, the government, AstraZeneca and CSL would need to finalise a formal agreement and production could proceed.</p>
<p>Even if AZD1222 is successful, the V451 clinical trials remain essential. V451 could potentially be more effective or better suited to specific groups, <a href="https://www.uq.edu.au/news/article/2020/08/urgent-call-older-queenslanders-volunteer-covid-19-study">especially older people</a>. It could also potentially be used to boost responses after AZD1222 vaccination. It’s a crucial card to have up our sleeve.</p><img src="https://counter.theconversation.com/content/145693/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Kylie Quinn 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 Australian government is working with two major pharmaceutical companies to facilitate the local production and supply of two different COVID-19 vaccines – if they’re proven to be effective.Kylie Quinn, Vice-Chancellor's Research Fellow, School of Health and Biomedical Sciences, RMIT UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/143592013-06-05T01:57:00Z2013-06-05T01:57:00ZCSL’s flu vaccine leaves a hole in Australia’s pandemic plan<figure><img src="https://images.theconversation.com/files/25044/original/6f35stqd-1370391118.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Not being able to give children the locally-manufactured vaccine leaves a hole in our pandemic preparations.</span> <span class="attribution"><span class="source">Julian Smith/AAP</span></span></figcaption></figure><p><em><strong>Facts about Flu</strong> - We often hear of an expected pandemic and had a scare in 2009 with the swine flu, but how well are we prepared?</em></p>
<p>Although no longer considered an immediate risk, the <a href="http://www.who.int/csr/don/2013_05_29/en/index.html">recent outbreak of bird flu</a> (H7N9) in China means pandemic planning is back on national agendas. A cornerstone of these plans is the early availability of vaccines - and Australia may have a problem. </p>
<p>Depending on when it becomes available, a pandemic vaccine should be targeted at those most at risk of a severe outcome from infection or at those who amplify its spread. </p>
<p>For both the seasonal and pandemic flu, the main spreaders are children. So a pandemic vaccine should be safe to give to children. Indeed, children, especially the very young, are one of the groups most at risk of <a href="http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5810a1.htm">severe outcomes</a>.</p>
<p>During the 2009 flu pandemic, Australia relied on local manufacturer CSL to produce a vaccine. After China, Australia was the second country in the world to have a pandemic vaccine available. It was given to both adults and children.</p>
<p>But CSL’s influenza vaccines are no longer recommended for children younger than five years and doubt exists about their safe use in children up to ten years old. </p>
<p>The change in recommendation by Australia’s <a href="http://www.nhmrc.gov.au/guidelines/publications/nic0043a">National Health and Medical Research Council</a> followed events in 2010, which had their genesis three years earlier.</p>
<h2>Questions about safety</h2>
<p>In 2007, a number of children in Western Australia died of influenza-related causes. So, the state government <a href="http://onlinelibrary.wiley.com/doi/10.1111/j.1750-2659.2010.00167.x/abstract">started a campaign</a> to provide free flu vaccines to children under the age of five. </p>
<p>CSL and other vaccine manufacturers provided vaccines at no cost. The first year of the campaign (2008) went well and the <a href="http://journals.lww.com/pidj/Abstract/2011/02000/Vaccine_Effectiveness_Against_Laboratory_confirmed.4.aspx">vaccine was assessed</a> as being about 60% effective, which is pretty much as expected. </p>
<p>No safety problems were recognised in 2008 or 2009, but things went horribly wrong in 2010.</p>
<p>In that year, the CSL flu vaccine – but not other registered vaccines – were found to have caused an unusually large number of high fevers. Some of these fevers were so severe that they <a href="http://bmjopen.bmj.com/content/1/1/e000016.abstract">led to fits</a>.</p>
<p>What’s more, some of the fits were prolonged and at least one resulted in <a href="http://www.theaustralian.com.au/news/features/virus-in-the-system/story-e6frg8h6-1226063484330">ongoing disability</a> in a previously healthy child. Following extensive investigation, the CSL vaccines are no longer recommended for children younger than five years old in Australia, the United Kingdom or the United States.</p>
<p>The events of 2010 probably couldn’t have been foreseen because the Fluvax seems to have been safe for children in some years but not others. It’s a problem CSL has yet to fully understand but, in retrospect, it <a href="http://www.sciencedirect.com/science/article/pii/S0264410X13004076">does not appear</a> to be isolated to 2010. </p>
<h2>Fevers and children</h2>
<p>CSL’s Fluvax was <a href="https://www.ebs.tga.gov.au/servlet/xmlmillr6?dbid=ebs%2FPublicHTML%2FpdfStore.nsf&docid=CDB8FE0FC46396A2CA257AF0003CBA98&agid=(PrintDetailsPublic)&actionid=1">first registered in Australia</a> for adults and children in 1991, at a time when formal studies of efficacy and safety were not routinely required. The vaccine was re-licensed for children in 2002, in a formulation that did not contain the preservative thiomersal, but was otherwise largely unchanged from the vaccine registered 11 years previously. </p>
<p>The regulator, Australia’s <a href="http://www.tga.gov.au/">Therapeutic Goods Administration</a>, refers to this method of registration as “grandfathering”. This implies the registration is based on confidence arising from widespread use or experience, but it’s not necessarily supported by formal evidence. </p>
<p>But grandfathering of Fluvax for children was done with almost no grandfatherly experience of its use in children. Although used widely in adults for many years, Fluvax was little used in children before the Western Australian campaign. </p>
<p>Because Fluvax was registered for children in Australia, it was <a href="https://www.mja.com.au/journal/2013/198/7/challenges-regulating-influenza-vaccines-children?0=ip_login_no_cache%3Da88ef0f843dc86ae09984d97357b1e83">registered for use in children</a> in a number of other countries – even though the Australian registration was not based on efficacy or safety data. </p>
<p>The <a href="http://www.lakemedelsverket.se/SPC_PIL/Pdf/par/Afluria,%20suspension%20for%20injection.pdf">international practice</a> of registering in one country when the vaccine was registered in another country was followed. It was only when Sweden requested safety data on the vaccine formulation without the thiomersal preservative that CSL conducted a safety and efficacy trial in children. This was done over two years in 2005 and 2006.</p>
<p>The <a href="http://onlinelibrary.wiley.com/doi/10.1111/j.1750-2659.2009.00108.x/abstract">results of this trial</a> were not published until 2009. And although not recognised at the time, they foreshadowed the problems of increased fever and related fits that were detected the following year. </p>
<p>At the request of US regulators, in 2009 CSL conducted a <a href="http://clinicaltrials.gov/ct2/show/NCT00959049?term=CSLCT-USF-07-36&rank=1">head-to-head comparison</a> of Fluvax with another US-registered influenza vaccine in children. Fluvax produced significantly more fevers than the other vaccine.</p>
<p>In another CSL-sponsored trial in Australia <a href="http://onlinelibrary.wiley.com/doi/10.1111/irv.12107/abstract">published this year</a>, the company’s 2009 southern hemisphere vaccine was found to be associated with high fever in children.</p>
<h2>A hole in the plan</h2>
<p>Fluvax was no longer recommended for young children after 2010, but it has been inadvertently given to children in Australia since. There was a <a href="http://www.news.com.au/breaking-news/banned-flu-vaccine-given-to-wa-children/story-e6frfkp9-1226335228864">serious adverse outcome</a> documented in the ACT only last year.</p>
<p>Given these ongoing problems, there may be reluctance to give any future pandemic influenza vaccine manufactured by CSL to children, unless it’s shown that benefits outweighed risks. And this leaves a potentially large hole in Australia’s pandemic plans.</p>
<p>To fill this hole, CSL would need to show it understood why its seasonal vaccines cause high fevers in children, at least in some years. The US Food and Drug Administration <a href="http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm259888.htm">has suggested the problem</a> is related, at least in part, to the CSL manufacturing process, and <a href="http://www.sciencedirect.com/science/article/pii/S0264410X12014272">CSL agrees</a>. </p>
<p>Even when the problem (known in the trade as the “root cause”) is identified, understood and fixed, CSL would need to conduct a very large trial of the improved vaccine to demonstrate its safety and efficacy. Only then could Australians once again feel confident about giving Fluvax to children. </p>
<p>Failing that, the nation will need to turn to other vaccine manufacturers to fill the hole in our pandemic plans. But this may mean there are insufficient doses available when the vaccine is most needed.</p>
<p><em>This is the fifth article in our series <strong>Facts about Flu</strong>. Click on the links below to read other instalments in the series.</em></p>
<p><strong>Part one</strong>: <a href="https://theconversation.com/of-influenza-flu-potions-and-key-opinion-leaders-14003">Of influenza, flu, potions and key opinion leaders</a></p>
<p><strong>Part two</strong>: <a href="https://theconversation.com/influenza-vaccine-for-2013-who-what-why-and-when-14050">Influenza vaccine for 2013: who, what, why and when?</a></p>
<p><strong>Part three</strong>: <a href="https://theconversation.com/h1n1-h5n1-h7n9-what-on-earth-does-it-all-mean-14815">H1N1, H5N1, H7N9? What on earth does it all mean</a></p>
<p><strong>Part four</strong>: <a href="https://theconversation.com/the-tamiflu-saga-shows-why-all-research-data-should-be-public-13951">The Tamiflu saga shows why all research data should be public</a></p>
<p><strong>Part six</strong>: <a href="https://theconversation.com/should-flu-shots-be-mandatory-for-health-care-workers-14039">Should flu shots be mandatory for health-care workers?</a></p>
<p><strong>Part seven</strong>: <a href="https://theconversation.com/the-holy-grail-of-influenza-research-a-universal-flu-vaccine-14046">The Holy Grail of influenza research: a universal flu vaccine</a></p>
<p><strong>Part eight</strong>: <a href="https://theconversation.com/is-it-really-the-flu-the-other-viruses-making-you-ill-in-winter-14895">Is it really the flu? The other viruses making you ill in winter</a> </p>
<p><strong>Part nine</strong>: <a href="https://theconversation.com/the-heart-of-the-matter-how-effective-is-the-flu-jab-really-14048">The heart of the matter: how effective is the flu jab really?</a></p><img src="https://counter.theconversation.com/content/14359/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Heath Kelly once attended a CSL vaccine meeting to discuss study design and will be attending a meeting in Valencia, Spain in June sponsored by Sanofi Pasteur. </span></em></p>Facts about Flu - We often hear of an expected pandemic and had a scare in 2009 with the swine flu, but how well are we prepared? Although no longer considered an immediate risk, the recent outbreak of…Heath Kelly, Professor (Adjunct) in Infectious Diseases Epidemiology, Australian National UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/34262011-09-18T02:24:03Z2011-09-18T02:24:03ZNew theory on why CSL’s flu vaccine caused febrile convulsions in children<figure><img src="https://images.theconversation.com/files/3670/original/aapone-20090924000206136276-nicola_roxon_swine_flu_vaccine-original.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Authors of a new paper suggest a detergent used by CSL in making its flu vaccine could be the cause of the problem.</span> <span class="attribution"><span class="source">AAP</span></span></figcaption></figure><p><em>A paper published in the Medical Journal of Australia today provides a possible reason for CSL’s 2010 flu vaccine causing febrile convulsions in children. The authors hypothesise that suboptimal use of the detergent called deoxycholate – used in the manufacturing process by CSL (one of the few vaccine manufacturers that use it) – to split the flu virus from its membrane may be at fault.</em> </p>
<p><em>Professor Anne Kelso, Director of the WHO Collaborating Centre for Reference and Research in Influenza, explains the manufacturing process of flu vaccines and provides the context for understanding the authors’ hypothesis.</em></p>
<p><strong>What goes into influenza vaccines and what’s the process of manufacturing? The paper describes CSL’s influenza vaccine as a trivalent vaccine so let’s start with that.</strong></p>
<p>A trivalent influenza vaccine has three components representative of the three types and subtypes of influenza viruses currently circulating in humans. Two of them are type A viruses (subtypes H1N1 and H3N2) and one of them is a type B virus. One of the type A viruses is H1N1 2009, the virus that caused the pandemic in 2009 and has continued to circulate in humans ever since. </p>
<p>Most influenza vaccines are made using eggs, which are injected with the live virus. The eggs enable the viruses to grow to a very high concentration. Manufacturers then purify the virus from the eggs and inactivate it – they kill it. There are a couple of different ways that companies do that and CSL uses one of these. </p>
<p>The next step is to “split” this preparation of inactivated virus. This is done by adding a detergent, which in CSL’s case is deoxycholate. This step separates the proteins in the virus from the membrane component – it basically takes the virus’s skin off. What you’re left with is an enriched preparation of virus protein.</p>
<p>The combination of the inactivation step and splitting step ensures that there is no live infectious virus in the preparation. People may think they can get a flu infection from the vaccine but that’s not possible because of the rigor with which these processes kill the virus.</p>
<p>Now, after inactivation, splitting and further purification, the virus preparation is in tiny pieces and enriched in one key protein of the virus which is necessary to induce immunity to influenza.</p>
<p><strong>What does this paper find was wrong with CSL’s influenza vaccine?</strong></p>
<p>The paper doesn’t come from an experimental study. Rather, it reviews existing literature. The authors have analyzed information in the public domain, including previous publications from other groups and what has been reported about the issues that arose in 2010 with the CSL vaccine, which caused febrile convulsions in some young children. </p>
<p>They’ve developed the hypothesis that the deoxycholate used in the splitting stage may be the critical difference between the CSL vaccine and other brands of vaccine that did not cause an elevated rate of febrile convulsions. </p>
<p>It’s an interesting and plausible hypothesis and a worthwhile contribution to the debate. The authors have reported circumstantial evidence in its support. But it’s also important to note that the authors themselves say that it’s speculative to implicate deoxycholate. </p>
<p>What I think they hope to do with the paper is stimulate investigation of the possibility that deoxycholate is one of the critical factors responsible for this vaccine causing febrile convulsions. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/3669/original/aapone-20090619000187825155-australia-health-flu-original.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/3669/original/aapone-20090619000187825155-australia-health-flu-original.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=388&fit=crop&dpr=1 600w, https://images.theconversation.com/files/3669/original/aapone-20090619000187825155-australia-health-flu-original.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=388&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/3669/original/aapone-20090619000187825155-australia-health-flu-original.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=388&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/3669/original/aapone-20090619000187825155-australia-health-flu-original.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=487&fit=crop&dpr=1 754w, https://images.theconversation.com/files/3669/original/aapone-20090619000187825155-australia-health-flu-original.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=487&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/3669/original/aapone-20090619000187825155-australia-health-flu-original.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=487&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">CSL needs to look at every step along its vaccine manufacturing process to find the cause of the adverse events.</span>
<span class="attribution"><span class="source">AAP</span></span>
</figcaption>
</figure>
<p><strong>Can CSL have been reasonably expected to know about any danger from the use of deoxycholate?</strong></p>
<p>There are many steps involved in manufacturing a flu vaccine. The company will have needed to look at every step along that pathway to consider whether there was something different about the way the vaccine was made in 2010 compared with other years, or about the way the manufacturing process worked with the viruses used in that vaccine.</p>
<p>CSL is now beginning to report their data. Some was reported at an influenza conference in Malta this week. I don’t know whether they have considered deoxycholate.</p>
<p>Although there are alternatives to deoxycholate, a company can’t just play around with the manufacturing process of a registered vaccine without testing the impact to make sure the vaccine is still safe and effective in humans. </p>
<p>This is where the interaction between companies and regulatory authorities is critical. Regulatory authorities ask to see all the data a company has on its vaccine to ensure it has all the properties it should before they allow that vaccine to be registered for use in their country. </p>
<p>In Australia, the regulatory authority is the Therapeutic Goods Administration (TGA) and in the United States it’s the Federal Drug Administration (FDA). </p>
<p><strong>FDA seems to have been more involved in highlighting the problems with CSL’s influenza vaccine rather than the TGA. Why is that?</strong></p>
<p>The FDA places a lot of information in the public domain. We know less about what TGA has said to CSL. </p>
<p>Different authorities take different approaches. TGA has made announcements about these problems on its website but we don’t know what it has said to the company.</p>
<p><strong>What impact do you think the paper will have?</strong></p>
<p>At the end of the paper, the authors have written that the benefits of vaccination to those at risk should not be lost in this analysis and I think that’s a very important point.</p>
<p>A second important point is that this paper represents the scientific process at work. </p>
<p>We can see the value of an open and transparent scientific system where data are available to anyone in the world so we can look for patterns like the one these authors are highlighting. It may be possible over time to see links or commonalities between different events that suggest an explanation for a new problem.</p><img src="https://counter.theconversation.com/content/3426/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health and Ageing. The Centre’s roles include influenza virus surveillance and isolation of viruses for use in influenza vaccines. Vaccine viruses are made available equally to all influenza vaccine manufacturers worldwide. The Centre also has collaborative research and development agreements with Novartis Vaccines & Diagnostics and the International Federation of Pharmaceutical Manufacturers and Associations. Anne Kelso owns shares in CSL Limited, which manufactures influenza vaccines among other products.</span></em></p>A paper published in the Medical Journal of Australia today provides a possible reason for CSL’s 2010 flu vaccine causing febrile convulsions in children. The authors hypothesise that suboptimal use of…Anne Kelso, Director, WHO Collaborating Centre for Reference and Research on InfluenzaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/19762011-06-23T04:32:21Z2011-06-23T04:32:21ZCSL gets warning shot from US drug regulator<figure><img src="https://images.theconversation.com/files/1825/original/aapone-20090924000206151981-australia-health-flu-vaccine-original.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">An FDA audit of CSL's laboratories has found the company doesn't follow good manufacturing practice.</span> <span class="attribution"><span class="source">AAP</span></span></figcaption></figure><p>The US <a href="http://www.fda.gov/">Food and Drug Administration (FDA)</a>, has just issued a <a href="http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm259888.htm">warning letter</a> about the safety of CSL’s influenza vaccine, Fluvax. The letter follows FDA’s latest annual inspection of <a href="http://www.csl.com.au/">CSL</a> laboratories and lays out five"objectionable conditions" in which the company has failed to comply with good manufacturing practice.</p>
<p>There was a major safety issue with CSL’s influenza vaccine, Fluvax, last year when it was found to cause unacceptably high rates of fever and febrile fits in young children. </p>
<p>One child in Western Australia may have suffered permanent brain damage. A Brisbane Coroner concluded that a link between the vaccination and death of a two-year old could neither be ruled in or ruled out. Fluvax caused fits in one in every 230 children vaccinated.</p>
<p>Then-chief medical officer, Professor Jim Bishop, made a <a href="http://test.tgpn.com.au/pdfs/JIM-BISHOP---FINAL-FLU-VAX-MEDIA%20RLSalert%20for%20under%205s.pdf">decision to suspend</a> all seasonal flu vaccines for children under five years old. Health departments across the states have noted that Fluvax was associated with 410 adverse reactions, including 67 cases of fits – all in children under the age of five. </p>
<p>The root cause of these reactions remains uncertain despite <a href="http://www.health.gov.au/internet/immunise/publishing.nsf/Content/immunise-factsheet-30jul10">several investigations</a> last year.</p>
<p>The FDA’s concerns relate both to the manufacturing process and how well CSL investigated the cause of Fluvax’s side effects. The Australian FDA equivalent, the <a href="http://www.tga.gov.au/">Therapeutic Drugs Administration (TGA)</a> said it had also sent letters to the company pointing out problems with CSL’s facilities uncovered by several audits.</p>
<p>CSL has responded to the FDA’s letter with a <a href="http://www.csl.com.au/s1/cs/auhq/1187378853299/news/1255926584811/prdetail.htm">statement on its website</a>, saying it has submitted a written response to the FDA to address the observations. The company says its response includes details of corrective steps it has already undertaken as well as further actions under way.</p>
<p>In its defence, CSL has worked openly with the TGA, Australian academics and colleagues at the <a href="http://www.cdc.gov/">US Center for Disease Control</a> to determine the reason for increased fever and fits in children.</p>
<p>Concerns centre over whether laboratory procedures ensure the flu virus has been adequately split or if a sub-component of the virus may be present in excess quantities. </p>
<p>The scientific evidence is not conclusive and lends some support to both ideas. If a flu vaccine is made out of whole viruses, it is likely to be both more reactogenic (likely to trigger side effects) and more immunogenic (conferring increased protection). </p>
<p>Good manufacturing processes are critical to product safety and it’s noteworthy that CSL’s safety record over decades had been good under both government and, later, private control. </p>
<p>Yet, the FDA and the TGA clearly require improvements. CSL is taking the matter very seriously and promising a rapid response. </p>
<p>The company has 15 days to provide a full formal response to the concerns raised in the FDA’s letter.</p>
<p>Although still licensed for children, the CSL influenza vaccine is not recommended for children under 5 at all and only recommended for children aged 5 to 9 if there is no alternative flu vaccine. </p>
<p>In the United States, the same vaccine, marketed as Afluria, is not recommended for children aged 9 or less.</p>
<p>Like Qantas, another highly respected Australian icon with a longstanding safety record, CSL needs to take stock, consult and invest in more checks and balances to optimise the safety of its vaccines for children here and abroad.</p><img src="https://counter.theconversation.com/content/1976/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Robert Booy is and has previously been a paid researcher on studies of the effect of CSL vaccines on children and adults. He has also spoken at CSL-sponsored events and received travel support from the company.</span></em></p>The US Food and Drug Administration (FDA), has just issued a warning letter about the safety of CSL’s influenza vaccine, Fluvax. The letter follows FDA’s latest annual inspection of CSL laboratories and…Robert Booy, Professor and Head of Clinical Research, National Centre for Immunisation Research and Surveillance, University of SydneyLicensed as Creative Commons – attribution, no derivatives.