Thread by @michaelzlin

Okay since everyone is asking about which booster to get, I decided to think about it quantitatively and arrived at some general conclusions.

1. If you're J&J or Pfizer, boost with Pfizer or Moderna (the 50mcg booster dose)
2. If Moderna, boost with any depending on your risk...

This supercedes anything I might have said earlier. Reasoning is as follows.

The NIH mix & match booster study tested all combinations in a neutralizing antibody assay where a level of 100 IU50/mL correlates with 91% protection pre-Delta

Preprint link
medrxiv.org/content/10.110…

If you're going to boost, seems might as well try to get to 90% protection again. We adjust for Delta requiring 4x higher antibodies to neutralize (consistent finding across many vaccines, some may remember). That makes 400 IU50/mL, the blue line below

Note it's a log scale so that's why the 400 line is where it is. Also I removed the Moderna 100mcg series (below) from the above graph because that won't be used for boosters. Just note it gives titres around 10³ = 1000, so Moderna 50mcg effects will be between Pfizer's and 10³

So if you're J&J or Pfizer, only Pfizer booster (or Moderna50 by extension) will get you to 400 (below image). Moderna50 might be better because we expect a slight drop between 15 and 29 days (above image).

If you're Moderna, any booster will get you to 400. So which to choose?

If you're Moderna and boost with J&J, you'll have slightly lower nAbs than if you chose Pfizer or Moderna50. But you might benefit if J&J activates a different set of T cells than Moderna did. One dose J&J did seem to elicit more T cells than 1 dose Pfizer

https://twitter.com/michaelzlin/status/1450420377130131459

If you're Moderna and boost with Pfizer you'll have higher nAbs, and if you boost with Moderna50 you'll have super-high nAbs. I tend to be suspicious of anything too high ("moderation in all things") so if I were healthy and Moderna I might choose J&J or Pfizer instead.

But if immunocompromised or otherwise higher risk, then Moderna+Moderna50 might be better. But if healthy, low-risk, and not too concerned about getting a mild breakthrough in the short term, then Moderna+J&J may lead to slightly better long-term immunity

These suggestions are not medical advice; each person's situation is different. The deductions above also don't account for conditions now being different from those of the study (3 mo post-vax whereas we're allowed boosters 6 mo post-vax).

But memory B cells, the ones stimulated by boosters, live long, so 6mo boosters are likely to give similar results as 3mo boosters. And Israeli data on Pfizer vax + Pfizer boost at 6mo show the return of strong protection against Delta, so there is some real-world calibration.

And more clinical correlation, from a randomized trial! Impressed Pfizer did a RCT with disease readout instead of just serology, or just letting Israel MOH do an epi study. Even more amazing: booster reduced cases by 96% compared to *vaxxed but unboosted*
pfizer.com/news/press-rel…

BTW, to be clear there's plenty of evidence that having super-high antibodies, e.g. 10x higher than what you get from 2x Moderna (primary series), is totally fine. How do we know? Because if you were previously infected then get a RNA vaccine (both doses) that's what happens.

For example this study shows 10x higher levels of antibodies and neutralizing activity among vaccine recipients prev infected vs not prev infected. That means may people have these super-high levels and they've been fine
science.org/doi/10.1126/sc…

Also, Moderna did show the Moderna vax + Moderna boost didn't have any safety signals (fda.gov/media/152953/d…). BTW they saw a 15-fold increase in nAbs vs preboost, but preboost is 3.3x lower at 6mo vs 1mo postvax, so that's a 5x increase postboost vs 1mo after original vax

When offered a choice of 3 things I usually take the middle one, but maybe that's just my temperament as a middle-child Gen-Xer. YMMV.