For the Ox/AZ vaccine, it's fairly simple. The trial demonstrated efficacy at a range of dose intervals. Antibody responses after the boost were significantly stronger with longer intervals - see table 3.https://www.gov.uk/government/publications/regulatory-approval-of-covid-19-vaccine-astrazeneca/information-for-healthcare-professionals-on-covid-19-vaccine-astrazeneca …
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(so in response to
@drmarkporter's point, higher immune responses with a longer interval is proven & now public. I haven't seen a similar analysis for efficacy against disease but the data exists and I suspect the regulators & JCVI committee have)6 replies 27 retweets 192 likesShow this thread -
For Pfizer, there isn't direct evidence of efficacy with a >3wk interval. But as widely publicised, efficacy in the period from 14 days after first dose to 21 days is high.pic.twitter.com/2f6QPyMg9a
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Can we extrapolate from this to a longer interval? It's a judgment call. On one hand is evidence-based medicine's scepticism of anything not directly proven 'beyond reasonable doubt' in an RCT; on the other is a 'balance of probabilities' approach based upon the biology.
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Based upon the biology, I'd eat my hat if the Pfizer vaccine is substantially less effective with a longer dose interval. Most vaccines induce stronger immune responses with longer intervals. A couple of examples below. There are more.pic.twitter.com/pxJTqjchpz
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Regimes like the Ox/AZ use the same adenoviral vector to prime & boost so face 'anti-vector immunity' (immunity from the first dose to the viral 'postman' which must delivers the spike protein 'message' for the boost). This favours longer intervals specifically for Ad/Ad but...
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...the above shows that longer intervals are better for regimes with different viral vectors, DNA priming, inactivated virus boosting - this isn't just an adeno effect. It's v rare for a 3wk interval to give stronger responses than 8+ wks (I can't think of examples, can you?)
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Mechanistically, at 3w, the immune response to prime isn't complete- it hasn't yet produced all the memory B cells which give the best response to the boost. Once they are made, the memory cells last years! They won't forget how to respond to a boost in a few months.
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I appreciate mechanistic arguments often prove to be wrong, and RCT evidence with Pfizer at longer intervals should definitely be produced ASAP... but as
@zeynep has written in an excellent article today: https://www.theatlantic.com/science/archive/2020/12/virus-mutation-catastrophe/617531/ …pic.twitter.com/NKMQGHorf8
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Replying to @sandyddouglas @zeynep
What is your opinion of the government's plan to use a different manufacturer for the second corona virus does, as explained in the NY times? Britain Opts for Mix-and-Match Vaccinations, Confounding Expertshttps://www.nytimes.com/2021/01/01/health/coronavirus-vaccines-britain.html?smid=tw-share …
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zeynep tufekci Retweeted zeynep tufekci
zeynep tufekci added,
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