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					<title>Why third jabs are inevitable</title>
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						<![CDATA[Tom Chivers]]>
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							<![CDATA[The Delta variant was a warning shot; we can't yet spare any vaccines. Credit: Amarjeet Kumar Singh/Anadolu Agency via Getty]]>
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							<![CDATA[<p><strong>Tom Chivers</strong> is a science writer. His second book, <em>How to Read Numbers</em>, is out now.</p>
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						<unherd:twitter_handle>TomChivers</unherd:twitter_handle>
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						<![CDATA[ is a science writer. His second book, <em>How to Read Numbers</em>, is out now.]]>
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										<pubDate>Mon, 14 Jun 2021 23:15:30 +0000</pubDate>
					<updated>Sat, 19 Jun 2021 09:34:04 +0000</updated>
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								<![CDATA[The variants are going to keep on circulating without another vaccine]]>
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								<![CDATA[<p><span style="font-weight: 400;">I am in uncharted waters. Next week, it will be one year since I had my first jab; I got my second in August 2020. I was on the AstraZeneca trial – I still am, until the end of this month – so </span><a href="https://unherd.com/thepost/im-on-the-oxford-vaccine-trial-heres-what-its-like/"><span style="font-weight: 400;">I got vaccinated before it was cool</span></a><span style="font-weight: 400;">. There’s almost no data on whether people who had the vaccine a year ago are still protected, for the simple reason that almost nobody had had the vaccine a year ago.</span></p>
<p><span style="font-weight: 400;">And the existing vaccines were designed to mimic the original strain of Covid. We’ve been broadly lucky so far – the vaccines all still work against the variants we’re aware of. But they work less well against the new Delta variant; </span><a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01290-3/fulltext"><span style="font-weight: 400;">a </span><i><span style="font-weight: 400;">Lancet </span></i><span style="font-weight: 400;">paper</span></a><span style="font-weight: 400;"> last month found that people who had had the Pfizer vaccine had a reduced immune response to the new variant, and </span><a href="https://khub.net/documents/135939561/430986542/Effectiveness+of+COVID-19+vaccines+against+the+B.1.617.2+variant.pdf/204c11a4-e02e-11f2-db19-b3664107ac42"><span style="font-weight: 400;">a recent Public Health England report </span></a><span style="font-weight: 400;">says that a single dose of either Pfizer or AstraZeneca only reduces the likelihood of infection by about 33%. </span></p>
<p><span style="font-weight: 400;">I don’t want to be too downhearted. It is worth remembering that even though we don’t have data from this vaccine, on the whole the immune system has an excellent memory, and vaccine protection usually lasts for years. And a double dose of either vaccine is much more effective, even against Delta: PHE says 60% in the AZ case, 88% with Pfizer. And they are much </span><i><span style="font-weight: 400;">more</span></i><span style="font-weight: 400;"> protective than those headline figures against severe disease and death: </span><a href="https://khub.net/web/phe-national/public-library/-/document_library/v2WsRK3ZlEig/view_file/479607329?_com_liferay_document_library_web_portlet_DLPortlet_INSTANCE_v2WsRK3ZlEig_redirect=https%3A%2F%2Fkhub.net%3A443%2Fweb%2Fphe-national%2Fpublic-library%2F-%2Fdocument_library%2Fv2WsRK3ZlEig%2Fview%2F479607266"><span style="font-weight: 400;">another PHE paper </span></a><span style="font-weight: 400;">finds that people who have had both jabs, of either vaccine, are more than 90% less likely to end up in hospital.</span></p>
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<p><span style="font-weight: 400;">But Delta is a warning shot. We might well see a new variant – I was going to say Epsilon, but apparently we’re </span><a href="https://en.wikipedia.org/wiki/Variants_of_SARS-CoV-2#Kappa:_Lineage_B.1.617.1"><span style="font-weight: 400;">already up to Kappa </span></a><span style="font-weight: 400;">– which escapes the vaccines even more effectively.</span></p>
<p><span style="font-weight: 400;">That&#8217;s why we need to start talking about third jabs.</span></p>
<p><span style="font-weight: 400;">If we want to maintain the freedoms we currently have, and certainly if we ever want to get rid of the disease, we are going to have to have a third innoculation. “The virus is very likely to remain endemic, for the next year at least,” says Dr Rupert Beale of the Crick Institute. Even with everyone double-jabbed, Delta is transmissible enough and vaccine-resistant enough to keep circulating. </span></p>
<p><span style="font-weight: 400;">The latest </span><a href="https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/993510/S1287_SPI-M-O_Summary_Roadmap_step_4.pdf"><span style="font-weight: 400;">SPI-M-O modelling</span></a><span style="font-weight: 400;"> suggests that it has an R</span><span style="font-weight: 400;">0</span><span style="font-weight: 400;"> of seven. (R</span><span style="font-weight: 400;">0</span><span style="font-weight: 400;"> is the number of people the average infected person spreads the disease to, in a population that has no immunity and no countermeasures against the disease.) If that’s true, then somewhere around 85% of people would need to be fully immune to reach herd immunity. With two jabs in every arm, we still wouldn’t reach that. In that situation it may not kill all that many people, but it will not go away, either. </span></p>
<div class="ref-ar"><a href="https://unherd.com/2021/05/who-isnt-getting-vaccinated/?edition=us&#038;ref=refinnar" class="text-decoration-none border-0"><a href="https://unherd.com/2021/05/who-isnt-getting-vaccinated/?edition=us&#038;ref=refinnar" class="text-decoration-none border-0"><img decoding="async" src="https://unherd.com/wp-content/uploads/2021/05/GettyImages-1230968844.jpg?w=300" /></a><div class="content"><a href="https://unherd.com/2021/05/who-isnt-getting-vaccinated/?edition=us&#038;ref=refinnar" class="text-decoration-none border-0"><span class="meta">More from this author</span></a><a href="https://unherd.com/2021/05/who-isnt-getting-vaccinated/?edition=us&#038;ref=refinnar" class="text-decoration-none border-0"><h5>Who isn&#039;t getting vaccinated?</h5></a><p class="author"><a href="https://unherd.com/2021/05/who-isnt-getting-vaccinated/?edition=us&#038;ref=refinnar" class="text-decoration-none border-0"><span>By</span> Tom Chivers</a></p></div></a></div>
<p><span style="font-weight: 400;">And it may still kill quite a few. Vaccinated people are protected from severe disease, but not perfectly: </span><a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01358-1/fulltext" target="_blank" rel="noopener"><span style="font-weight: 400;">another <em>Lancet</em> paper </span></a><span style="font-weight: 400;">suggests that the risk of hospitalisation, if you get the disease, is about a quarter what it would be if you weren’t. </span><a href="https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/993510/S1287_SPI-M-O_Summary_Roadmap_step_4.pdf"><span style="font-weight: 400;">SPI-M-O suggests</span></a><span style="font-weight: 400;"> that an uncontrolled third wave could cause hundreds of deaths a day by autumn, even though almost everyone would be double-jabbed, hence Monday’s announcement of the delay to the roadmap.</span></p>
<p><span style="font-weight: 400;">So we need to talk about what the strategy should be.</span></p>
<p><span style="font-weight: 400;">So for starters, should we wait for variant-specific vaccine updates? The pharma companies aren’t idiots: they’ve already started creating vaccines for the Alpha to Delta variants. The mRNA vaccines, such as Pfizer and Moderna, are especially quick to turn around, since you can code a new one almost like computer software. </span></p>
<p><a href="https://www.greenlightbiosciences.com/blog/amin-khan-welcomed-as-chief-scientific-officer-human-health/" target="_blank" rel="noopener"><span style="font-weight: 400;">Amin Khan</span></a><span style="font-weight: 400;">, head of vaccines at the biotech firm GreenLight[1. Full disclosure: I’ve done some paid work with GreenLight during the pandemic]</span><span style="font-weight: 400;">, says that you can get a new variant-specific mRNA vaccine ready to go in a few weeks. And if the new version simply targets a slightly modified version of the spike protein, as the existing vaccines do, it won’t need much in the way of testing and regulatory approval. Changing your manufacturing system is more complicated, “but within two or three months, you can get a new variant to the market”.</span></p>
<p><span style="font-weight: 400;">Playing whack-a-mole with new variants isn’t a long-term solution, though. The hope is that “third-generation” vaccines will be capable of covering all the existing variants and most foreseeable future ones. But, says Khan, that’s a bit more complicated. A more complete version might target other parts of the virus than the spike protein; that would mean a much more rigorous testing and approval regime, and it may take months longer to get such a vaccine to market. </span></p>
<p><span style="font-weight: 400;">We needn’t necessarily wait for a third-generation vaccine to start giving boosters, though. There is good reason to think that a third jab of an existing vaccine will provide a boost to protection, and there’s </span><a href="https://www.uhs.nhs.uk/AboutTheTrust/Newsandpublications/Latestnews/2021/May/Southampton-leads-world-first-Covid-19-vaccine-booster-study.aspx" target="_blank" rel="noopener"><span style="font-weight: 400;">an ongoing trial</span></a><span style="font-weight: 400;"> at the University of Southampton to see whether that’s true — but it is true for other vaccines, so it’s probably true for Covid.</span></p>
<p><span style="font-weight: 400;">Assuming that it does offer greater protection, the </span><i><span style="font-weight: 400;">next</span></i><span style="font-weight: 400;"> question is whether the booster jab should be the same vaccine you’ve already had, or a new one. Again, there are </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3743086/" target="_blank" rel="noopener"><span style="font-weight: 400;">theoretical reasons</span></a><span style="font-weight: 400;"> to think that a different (“heterologous”) booster from the one you’ve already had might provide greater protection. But “there’s no substitute for large amounts of data”, says Beale. </span></p>
<div class="ref-ar"><a href="https://unherd.com/2021/06/why-we-should-welcome-the-lab-leak-theory/?edition=us&#038;ref=refinnar" class="text-decoration-none border-0"><a href="https://unherd.com/2021/06/why-we-should-welcome-the-lab-leak-theory/?edition=us&#038;ref=refinnar" class="text-decoration-none border-0"><img decoding="async" src="https://unherd.com/wp-content/uploads/2021/06/toxic-1-scaled.jpg?w=300" /></a><div class="content"><a href="https://unherd.com/2021/06/why-we-should-welcome-the-lab-leak-theory/?edition=us&#038;ref=refinnar" class="text-decoration-none border-0"><span class="meta">Suggested reading</span></a><a href="https://unherd.com/2021/06/why-we-should-welcome-the-lab-leak-theory/?edition=us&#038;ref=refinnar" class="text-decoration-none border-0"><h5>Why we should welcome the lab leak hypothesis</h5></a><p class="author"><a href="https://unherd.com/2021/06/why-we-should-welcome-the-lab-leak-theory/?edition=us&#038;ref=refinnar" class="text-decoration-none border-0"><span>By</span> Bret Weinstein</a></p></div></a></div>
<p><span style="font-weight: 400;">At the moment there isn’t much data. A </span><a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01115-6/fulltext" target="_blank" rel="noopener"><i><span style="font-weight: 400;">Lancet</span></i><span style="font-weight: 400;"> paper</span></a><span style="font-weight: 400;"> came out recently which found that a heterologous boost had greater “reactogenicity” – that is, it caused more of the mild, expected side effects (feverishness, headache, joint pains) that tell you a vaccine is probably working – than a same-vaccine jab, while also finding no severe adverse reactions. So that’s promising, as are </span><a href="https://www.sciencemag.org/news/2021/06/mixing-covid-19-vaccines-appears-boost-immune-responses" target="_blank" rel="noopener"><span style="font-weight: 400;">a few other studies</span></a><span style="font-weight: 400;">. </span></p>
<p><span style="font-weight: 400;">And the Southampton trial </span><a href="https://www.covboost.org.uk/about" target="_blank" rel="noopener"><span style="font-weight: 400;">will be assigning</span></a><span style="font-weight: 400;"> people one of seven different vaccines at random, so it should naturally show if there’s a significant difference between using the same jab and using a different one. That said, it has a relatively small sample size (about 3,000 people, divided between seven Covid vaccines and a control), so it may not be powerful enough to detect small differences. </span></p>
<p><span style="font-weight: 400;">One thing that might be worth trying is letting people say that they’re happy to take a heterologous third dose at their own risk; I (for instance) would be quite happy to take a Pfizer or Moderna jab on top of my two AZ doses, and accept the risk of any negative consequences, because I’m extremely confident that there wouldn’t be any. And if a few hundred thousand people did that, then we would soon get some good data on the effectiveness of the strategy.</span></p>
<div class="ref-ar"><a href="https://unherd.com/2020/11/why-is-france-full-of-anti-vaxxers/?edition=us&#038;ref=refinnar" class="text-decoration-none border-0"><a href="https://unherd.com/2020/11/why-is-france-full-of-anti-vaxxers/?edition=us&#038;ref=refinnar" class="text-decoration-none border-0"><img decoding="async" src="https://unherd.com/wp-content/uploads/2020/11/GettyImages-93004988-e1605197217800.jpg?w=300" /></a><div class="content"><a href="https://unherd.com/2020/11/why-is-france-full-of-anti-vaxxers/?edition=us&#038;ref=refinnar" class="text-decoration-none border-0"><span class="meta">Suggested reading</span></a><a href="https://unherd.com/2020/11/why-is-france-full-of-anti-vaxxers/?edition=us&#038;ref=refinnar" class="text-decoration-none border-0"><h5>France is infected with anti-vaxxers</h5></a><p class="author"><a href="https://unherd.com/2020/11/why-is-france-full-of-anti-vaxxers/?edition=us&#038;ref=refinnar" class="text-decoration-none border-0"><span>By</span> John Lichfield</a></p></div></a></div>
<p><span style="font-weight: 400;">Most likely, it will turn out that it’s best to do heterologous boosting. Not only might it be more effective, but it reduces the logistical difficulties of finding the right dose for the right person. A really crucial thing should be that we drop the restrictions on using the AstraZeneca vaccine in the under-40s; if we’re going to accelerate second jabs, let alone consider doing thirds, we’re going to need it.</span></p>
<p><span style="font-weight: 400;">The third question is who we should be giving it to. There is, as I understand it, good evidence that, insofar as vaccine-induced immunity gets weaker over time, it gets weaker fastest in the old; and since the old are the most vulnerable, it makes sense to boost from the eldest to the youngest again. I might add one detail, though, which is that since there is a clear difference in protection against Delta — at least according to the PHE data — between the Pfizer and the AstraZeneca vaccines, it may be worth preferentially giving boosters to people who had Ox/AZ. </span></p>
<p><span style="font-weight: 400;">And the last question is: when? </span></p>
<p><span style="font-weight: 400;">This is complicated; we need data. But assuming there is a real boost in protection from a third jab in people whose first jab was six months ago or more, then we probably need to start thinking about giving those elderly and vulnerable people the boost in the next couple of months. Professor Saul Faust, who heads the Southampton trial, says that the JCVI will make decisions in August or September, by which time the first vaccines will have been in people’s arms </span><a href="https://www.bbc.co.uk/news/av/health-55227833" target="_blank" rel="noopener"><span style="font-weight: 400;">for nine or 10 months</span></a><span style="font-weight: 400;">. </span></p>
<p><span style="font-weight: 400;">If the UK hits its target of giving every adult a first dose by the end of July, then every adult should have had a second dose by the end of September or early October. Whether we ought to start giving third doses to the elderly before we give second doses to younger groups – or even whether we vaccinate children beforehand – is a question that can only be answered with a cost-benefit analysis, looking at how many lives (or rather years of life) we can expect to save with each. Until some actual data is in from the Southampton trial and others, we can’t reasonably do that analysis.</span></p>
<p><span style="font-weight: 400;">There’s another question, of course. Can we reasonably justify giving third doses to British citizens when billions of people around the world haven’t had a </span><i><span style="font-weight: 400;">first </span></i><span style="font-weight: 400;">dose? From a global perspective, </span><a href="https://unherd.com/2021/04/india-needs-our-vaccines/" target="_blank" rel="noopener"><span style="font-weight: 400;">the answer is obvious</span></a><span style="font-weight: 400;">: a life in Malawi or Sri Lanka is worth no less than a life in the UK and should be given equal value. I instinctively want to say that we should throw huge amounts of money and all our spare vaccines into GAVI and Covax.</span></p>
<p><span style="font-weight: 400;">But from a UK government perspective, it’s not so clear. “The first duty of the Government is to afford protection to its citizens,” goes the axiom. If you hire a babysitter, you are paying that babysitter to look after your child, rather than every child in the world.</span></p>
<p><span style="font-weight: 400;">This doesn’t extend to a complete disregard for lives in other nations. If a babysitter saw a child drowning across the street, I think most of us would think it was justified for them to rush out and save it even if it meant leaving your child unattended for a few minutes; at some point, a large chance to save a life in the developing world outweighs a small risk to a life in your own country. But it is at least not </span><i><span style="font-weight: 400;">obvious</span></i><span style="font-weight: 400;"> that, from a national government’s point of view, the right thing to do is share vaccines equitably. </span></p>
<p><span style="font-weight: 400;">Most likely, I’m still well protected against Covid, including the Delta variant. But whether that will still be true by the time the Lambda, Upsilon, Pi and Omega variants arrive is not clear; each new variant that arrives is a new chance for it to escape the vaccines more effectively. </span></p>
<p><span style="font-weight: 400;">This is still uncharted water. We need to chart them, as quickly as possible, and to get third jabs into people who need them, so that we can keep on opening up and not slide back into the dark days. I’ve </span><a href="https://www.covboost.org.uk/participate" target="_blank" rel="noopener"><span style="font-weight: 400;">put my name down</span></a><span style="font-weight: 400;"> for the Southampton trial.</span></p>
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