Sandy Douglas Profile picture
Jan 1, 2021 12 tweets 5 min read Read on X
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. Image
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. Image
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… Image
There is a good debate:
@Bob_Wachter has written thoughtfully

@trishgreenhalgh @EricTopol @nataliexdean have all argued the other way from me - would welcome their thoughts on the above 🧵
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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More from @DouglasVaccines

May 6, 2021
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.

Moderna said in Oct 20 they wouldn't enforce patents- why's nobody else making that vac yet?🧵
investors.modernatx.com/news-releases/…
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.
Read 10 tweets
Mar 1, 2021
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).

khub.net/documents/1359…

This is symptomatic infection in over 70s (BNT162b2=Pfizer): Image
I wrote about the Scottish data, and challenges of interpreting this sort of study, yesterday.

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). Image
Read 7 tweets
Feb 28, 2021
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).
Read 20 tweets
Jan 31, 2021
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/
I proposed what’s shown here.
Read 17 tweets
Jan 31, 2021
Amazing news. Our team @JennerInstitute are so pleased to see this!

A few quick responses to some pointing out it could be even better (more/cheaper/single-dose) 1/
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/
Read 9 tweets
Jan 30, 2021
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/
Read 8 tweets

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