The science of COVID-19 booster vaccines 🧵

Will the boosters works?
Yes.
They work really well. Great clinical trial results.
Antibody levels go back to peak or 4x more, and the booster teaches your immune system to recognize Delta even better.

Many vaccines are 3-doses
You will also probably have more durable immune memory after the COVID vaccine booster (including antibodies, CD4 T cells, CD8 T cells, and memory B cells). Not guaranteed, but likely.
That's because your immune system is basically a cost:benefit analysis machine.
Immune memory / protective immunity has a real caloric cost over time. If your immune system sees something once, it doesn't tend to commit much energy into making memory and sustaining all of those antibodies. But if your immune system sees an infection 3 times (or a vaccine)…
the immune system thinks "Wow, I keep getting infected with this! That sucks. Let's put up better defenses,” and sustains more antibodies, memory T cells, and B cells, at closer to peak levels.

Discussed more here:
Lots of vaccines are 3-dose regimens. Then with boosters every 10 years.
The hope was for it to be simpler for COVID, but that maybe hasn't worked out with Delta variant. Delta is tougher to stop. It is so transmissible.
The original coronavirus wasn't that hard for the immune system to stop, and 2-doses of vaccine worked amazing --even 1-dose was good. Most vaccines are a 3 dose regimen.
Will your immune system recognize other variants after a booster?
Yes.
The immune response becomes broader after the booster vaccination
Similar to what is talked about here.
science.sciencemag.org/content/372/65…
And has been shown in a series of memory B cell papers since then.
And the general topic here.
scientificamerican.com/article/your-i…
Adding to this thread the actual immune response data on boosters, for easy access. Moderna booster trial results were reported in May. 50mcg dose (Half dose) of original mRNA-1273, or Beta variant booster. In a full preprint: medrxiv.org/content/10.110…
Antibody data. No T cell data
Pfizer results are only available as a slide. Antibody data. No T cell data.

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More from @profshanecrotty

14 Sep
Our newest study is out in Science!
It cover 5 COVID-19 RNA vaccine topics. Using samples from the "low dose" 25mcg Moderna RNA COVID-19 vaccine clinical trial 🧵👇🏼
science.org/doi/10.1126/sc…
By the LJI team! @Dani6020 @SetteLab @jmateust @ljiresearch
The five finding summarized here:
🔵  T cell memory to an RNA vaccine at 7 months
🔵  Vaccine dose sparing (25mcg v 100mcg)
🔵  Vaccine v. natural immunity
🔵  T cell memory with age
🔵  Pre-existing crossreactive memory T cells: Do they do anything?
🔵  T cell memory to an RNA vaccine:

Impressive T cell memory at 7 months (6 months after 2nd dose). CD4s & CD8s. Tfh & cytokine+.

Overall, looks like two doses of an RNA vaccine generates impressive T cell memory that is likely to last for many years.
Even 25mcg Moderna dose
Read 12 tweets
31 Aug
Just a friendly reminder that this study also addressed natural immunity compared to vaccine immunity. Vaccine immunity did somewhat better than natural immunity, including against Delta. Image
In that large, carefully done, prospective, longitudinal study in the UK of over 300,000 people with regular testing, both vaccine immunity and natural immunity showed significant protection against COVID-19, with vaccine immunity doing somewhat better than natural immunity. ImageImage
As a prospective study, with a randomization component, the conclusions have higher confidence compared to some other studies. including against Delta.
Read 4 tweets
21 Aug
Boosters+global equity:
Practically speaking, the US should continue to retain enough doses to vaccinate all unvaccinated Americans. But resistance to vaccination remains high, so there is probably little to no real cost in allowing Americans who want boosters to get a 3rd dose
The USA has to keep trying hard to vaccinate the unvaccinated. But many of those reserved doses will likely expire otherwise, sadly.

Discussed some in the chat with @CarlosdelRio7 @Bob_Wachter at the end
Any vaccine dose given to an unvaccinated American is FAR more valuable than a 3rd dose given to a vaccinated American. For preventing deaths, hospitalizations, cases, and transmissions.
washingtonpost.com/outlook/corona…
Read 7 tweets
20 Aug
I have no problem with boosters allowed at 8 months for people who want them.

Is there American data indicating waning immunity against Delta? No. Nothing substantial.

Is there uncertainty about protective efficacy against Delta COVID-19 at 6 months? Yes 🧵
The COVID vaccines are incredible--they have exceeded all expectations. But, Delta is tougher to stop. It is so transmissible. The original coronavirus wasn't that hard for the immune system to stop, and 2-doses of vaccine worked amazing.
2-dose gives overall good immune memory. New Moderna science paper on antibodies at 6 months. Our T cell data. Multiple memory B cell data. The COVID vaccines have worked incredibly well! Six month clinical trial efficacies of 91% and 93%.
Read 12 tweets
20 Aug
A very large, well designed study of vaccine efficacy in UK in during Delta or Alpha. 🧵
Take home messages:
🔵 ~86% Pfizer protection from Delta infections Ct < 30
🔵  Peak Delta viral RNA in infected vax and unvaxxed were similar  
🔵  Some evidence of declining immunity
The preprint:
ndm.ox.ac.uk/files/coronavi…
There is a ton in this.
🔵 ~86% Pfizer protection from Delta infections Ct < 30

I very much agree with biostatistics Prof Shiela Bird that focusing on cases with Ct<30 makes sense in these types of surveillance studies. Pfizer Delta protection was 86%, AZ was 69% (Table 2). bit.ly/3sAeqd8
Read 18 tweets
6 Aug
A huge J&J COVID-19 vaccine study has just been released this morning, including Delta variant cases. ~500,000 person study in South Africa! A careful and well done clinical study by an amazing team, including Glenda Gray.
Take home messages: 🧵
Take home messages:
🔵 ~93% protection from death
🔵  ~71% protection from Delta variant hospitalizations
🔵  Large study
🔵 ~93% protection from death
Clear result. Covers both the Beta variant period and the Delta variant period. Looks to be equal against both.
Read 7 tweets

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