THREAD
There’s much debate around the UK's recommended use of the AZ vaccine with a two-dose schedule and flexible timing of second dose. Some thoughts on the AZ recommendation (not Pfizer) based on available data with refs to some excellent threads.

UK’s MHRA and JCVI are highly-experienced in vaccine assessments and recommendations, and they've surely weighed the benefits & risks of this recommendation carefully. That said, it would be good to see all the data underpinning their recommendation. 2/
https://t.co/NRcHbYxRIw
In general, vaccines should be taken on a schedule tested in an efficacy trial. But it wasn’t possible to conduct the typical dose and schedule optimization prior to these Ph3 trials, and those trials provided valuable data to inform these recommendations. 3/
The UK recommends a two-dose schedule, with the second dose between 4-12 weeks. This *is not* a single dose schedule. Given the data provided, and in the setting of limited supply, overstretched hospitals, and emergence of a more transmissible variant, this seems justifiable. 4/
The UK has important data on the AZ Vx that wasn’t available for Pfizer & Moderna at FDA's VRBPAC, including:
* single-dose efficacy through 4+ months; and
* single-dose immunogenicity (12+ weeks). 5/
https://t.co/vtbviE9VEx
The data shows the AZ vaccine maintains efficacy in the setting of a delayed second dose, although it’s not clear how fast this wanes over time. Delay of the second dose provides a better booster effect as measured by antibody levels, which is seen with other vaccines. 6/
The second dose is important because it can drive a more robust and higher quality antibody response through a process called affinity maturation. It's well-understood that longer intervals can provide a better boost. 7/ https://t.co/cqKIpomUHg
In my view, the immediate priority is prevention of severe disease that drives deaths and the strain on health systems. Efficacy against severe disease is likely better than overall vaccine efficacy. Data after the first dose is promising although the numbers are small. 8/
There’s nothing magic about the (short) 28d interval between doses, which was presumably chosen to ensure rapid onset of protection in Ph3. Vaccine efficacy won't disappear overnight with a delayed 2nd dose - it will wane over time, if at all. Ph3 data supports that concept. 9/
Yes there are risks of waning immunity, non-compliance with the second dose, confusion among the public, etc. Many are implementation considerations that can be addressed with planning and strong communication. 10/
It will be critically important to collect efficacy data around this “flexible second dose” schedule, esp in older adults & against severe disease, to inform licensure and recommendations in countries around the world that are counting on the introduction of this vaccine. 11/
Yes the AZ/Oxford studies had a number of issues, but we must remember that this highly-complex development program was executed in less than a year. And that Pfizer & Moderna's Ph3 execution & vaccine efficacy created very high expectations for all subsequent programs. 12/
The bottom line is that every country needs to make difficult policy decisions with the data they have, not what they'd like to have. There's no perfect answer here, but now that a decision has been taken, the UK can focus on maximizing the benefit and mitigating any risks. 13/

More from Government

Long thread: Because I couldn’t find anything comprehensive, I’m just going to post everything I’ve seen in the news/Twitter about Trump’s activities related to the Jan 6th insurrection. I think the timing & context of his actions/inactions will matter a lot for a senate trial.

12/12: The earlier DC protest over the electoral college vote during clearly inspired Jan 6th. On Dec 12th, he tweeted: “Wow! Thousands of people forming in Washington (D.C.) for Stop the Steal. Didn’t know about this, but I’ll be seeing them! #MAGA.”


12/19: Trump announces the Jan. 6th event by tweeting, “Big protest in D.C. on January 6th. Be there, will be wild!” Immediately, insurrectionists begin to discuss the “Wild Protest.” Just 2 days later, this UK political analyst predicts the violence


12/26-27: Trump announces his participation on Twitter. On Dec. 29, the FBI sends out a nationwide bulletin warning legislatures about attacks https://t.co/Lgl4yk5aO1


1/1: Trump tweets the time of his protest. Then he retweets “The calvary is coming” on Jan. 6!” Sounds like a war? About this time, the FBI begins visiting right wing extremists to tell them not to go--does the FBI tell the president? https://t.co/3OxnB2AHdr

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A brief analysis and comparison of the CSS for Twitter's PWA vs Twitter's legacy desktop website. The difference is dramatic and I'll touch on some reasons why.

Legacy site *downloads* ~630 KB CSS per theme and writing direction.

6,769 rules
9,252 selectors
16.7k declarations
3,370 unique declarations
44 media queries
36 unique colors
50 unique background colors
46 unique font sizes
39 unique z-indices

https://t.co/qyl4Bt1i5x


PWA *incrementally generates* ~30 KB CSS that handles all themes and writing directions.

735 rules
740 selectors
757 declarations
730 unique declarations
0 media queries
11 unique colors
32 unique background colors
15 unique font sizes
7 unique z-indices

https://t.co/w7oNG5KUkJ


The legacy site's CSS is what happens when hundreds of people directly write CSS over many years. Specificity wars, redundancy, a house of cards that can't be fixed. The result is extremely inefficient and error-prone styling that punishes users and developers.

The PWA's CSS is generated on-demand by a JS framework that manages styles and outputs "atomic CSS". The framework can enforce strict constraints and perform optimisations, which is why the CSS is so much smaller and safer. Style conflicts and unbounded CSS growth are avoided.