This issue is, appropriately, contentious. As a vaccinologist - & citizen & relative of people in at-risk groups - I fully support the UK decision to increase dose intervals of both our Ox/AZ product and the Pfizer product. I'd happily receive either with a >8w gap. Here's why 🧵
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. gov.uk/government/pub…
(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)
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.
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.
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.
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...
...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?)
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.
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: theatlantic.com/science/archiv…
There is a good debate: @Bob_Wachter has written thoughtfully
I haven't yet seen a vaccine immunologist who has personally done experiments giving vaccines at different intervals and who is concerned about the longer interval... but I look forward to hearing that view too...
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I'm not sure real impact of US vaccine patent announcement will match political/headline effect - it's a distractor from equitable distribution of vaccine now.
Patent waivers were effective for HIV drugs, but they are simple chemicals - the patent is the key barrier to a company starting to make them.
Vaccines are made in complex biological processes. Issues include 1. Non-patent know-how 2. Supply chain 3. Product consistency
Know-how: A patent covers only a tiny fraction of what you need to know to make a vaccine. Setting up a new facility to make a vaccine ('tech transfer') requires 1000s of pages of documentation & months of v active engagement from people who already understand the tech in depth.
Further UK observational data (last week Scotland, now England) looks encouraging for both ChAdOx & Pfizer vaccines in elderly population (1 dose, vs symptomatic infection and hospitalisation).
Can't be sure yet but 2 data sets now show plateauing / perhaps some waning of efficacy of a single dose of the Pfizer product from day 35 on - shown above in English data in terms of odds ratio (low = good) and below in Scottish data as vaccine efficacy (high = good).
Two Qs & a 🧵re evolving data on Ox/AZ vaccine effectiveness 1. Can anyone still reasonably doubt safety/efficacy, incl one-dose/ over 65? 2. Has anyone written a good critique of possible biases in the Scottish effectiveness data? papers.ssrn.com/sol3/papers.cf… @nataliexdean ?
The Scottish data is an observational study led by @EdinburghUni of >300k recipients of single doses of each of Pfizer & Ox/AZ vaccines, looking at effect on hospitalisation with COVID-19.
I graphed the headline results (from tables 2 & 3). Both vaccines look very good.
Ox/AZ recipients were older, median age perhaps ~75. Est 94% efficacy of any vaccine in this population is pretty amazing. Efficacy in over 80s isn't broken down by vaccine but will be mostly the effect of Ox/AZ vaccine (despite somewhat longer follow-up on Pfizer recipients).
There’s a bit more back story that's probably worth having in the public domain re AZ/Ox vaccine supply to UK & EU.
These 🧵👇 explained the tech & funding.
Some are saying ‘a contract (re dose allocation ) is a contract’ – but there’s more to it than meets the eye... 1/
I haven’t seen the AZ-EU/AZ-UK contracts. They may be unwise, I don’t know.
What I do know is that in Mar, I & my team @JennerInstitute developed what became the UK supply chain (and India/China). In Apr, *before AZ deal*, @GovUK Vacc Taskforce wanted a plan for UK supply. 2/
The Ox/AZ/SerumInst deal is incredibly radical- Ox opted out of £££ to make a brand new product available around the world not-for-profit. Please judge imperfections by comparison to Pfizer/Moderna, not vs an imaginary ideal or a company which hasn’t yet delivered any doses.
Quibble #1: ‘It needs 2 doses’. Ox/AZ haven’t done as good a PR job on this as J&J, but the vaccines are similar. Published Ox data shows substantial single dose efficacy if you read tables carefully. Further analysis will be done soon. 2/
Great thread explaining the background re AZ vaccine supply - UK government didn't just buy some doses, it paid >90% of the cost of developing the vaccine, including a complex new manufacturing process developed by our group. 1/
We & @AstraZeneca worked all year in anticipation of this scarcity & nationalism. We developed a strategy which gives as many countries / regions as possible control over their own supply AND aims to provide vaccine for export. 2/
That's why AZ's network is now making vaccine in at least 12 countries 👇. The problems at EU contractors are extremely unfortunate but as Adam's 🧵explains, each site is getting to grips with a v complex process, having started at different times. That involves uncertainty. 3/