Another study just posted comparing Abs & T cells in #JnJers after J&J, Moderna100, or Pfizer boost

Confirms NIH and Singapore studies: Both Abs and T cells are boosted by Moderna100 > Pfizer > J&J

#JnJers should boost accordingly

h/t @ChildrenNeedUs_

medrxiv.org/content/10.110…
Booster happened at 3mo after J&J vaccination.

Fig 2A: Antibody levels after boost go as Moderna100 > Pfizer > J&J

Moderna50 would be in between Moderna100 and Pfizer, most likely Image
Fig 2B: p values were not done for differences in post-boost antibody levels by booster group, but for diffs in fold change within individuals by booster group. Subtle distinction, but the latter is more variable (boxes and whiskers are taller). Anyway all diffs significant. Image
Why would fold change in antibody levels after boosting be a more variable measurement than antibody levels in the study population? Probably because if you have lower antibodies preboost you can have a big change, and if you have higher levels preboost you may get less change.
Fig 2C: neutralizing antibody levels. ULoD = upper limits of detection; Moderna and Pfizer effects are literally off the charts Image
Fig 3A: Here they use IFN as a measure of T cell activation by spike protein. The Moderna100- and Pfizer-boosted T cell activity levels are higher average than the J&J-boosted level. Also a larger fraction of the J&J-boosted failed to mount a response above the positive threshold Image
Note the p values (numbers under the gray boxes) are all small, so all diffs are "stat sig". Doesn't mean the results are equally good in clinical or biological significance. P values provide a measure of confidence a difference exists, not the usefulness of the difference
Fig 3B: p values calculated not for diffs between boosters in post-boost T cell levels, but for fold change within individuals by booster (which again looks more variable). J&J vs Moderna100 booster is significant at the 5% level; J&Js v Pfizer booster is not. Image
Conclusions: 1) If you're J&J, boosting with Moderna100 or Pfizer gives higher Ab levels than boosting with another J&J. Moderna50 should be in between Moderna100 and Pfizer. 2) Pretty clear that boosting with Moderna100 or Pfizer gives more T cells than boosting with J&J too.*
*Some might try to argue that "there's no evidence that Pfizer boost is better than J&J boost for T cell function" because of Fig 3B. But this high-variance metric still trends Pfizer > J&J. Also in Fig 3A, J&J + J&J has a higher rate of no detectable T cell responses
Real-life implication: If you're J&J, you're best off boosting with Moderna50 (by interpolation), followed by Pfizer, then J&J for both antibodies and T cell function. This confirms our earlier conclusion from the the NIH and Singapore studies

P.S. noting again that lower effectiveness of J&J booster vs Pfizer booster here may be partly due to anti-adenovirus antibodies from the initial J&J vaccination clearing some particles from the J&J booster before they can infect cells

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More from @michaelzlin

25 Oct
We can compare the UK experience to other similar countries to understand the role of public health rules in limiting disease.

Here I choose the Netherlands for comparison since it is close geographically, has similar vaccine rates, and had an initial Delta surge of similar size Image
As apparent from the graph above, UK doesn't come out too well. But first let's establish the conditions. Vaccination rates are similar between UK and Netherlands Image
Age structure is similar with the Netherlands having slightly more people in age segments >50yo ImageImage
Read 22 tweets
23 Oct
Pfizer's application for the vaccine for 5-11yo is progressing well.

FDA analysis identifies no red flags.

cnbc.com/2021/10/23/fda…
VRBPAC meeting Tuesday to discuss risk/benefit ratio. Much will depend on the value of case suppression which I think should be considered in context of schools and families. Meeting materials at link below

fda.gov/advisory-commi…
Trial was too small (n ~ 1500 in vaccine group) to see myocarditis. FDA estimated benefits vs risks assuming MC rate similar to 12-17yo getting 30ug (maybe overestimate; 5-11yo get 10ug).
Read 6 tweets
21 Oct
You mean high yield like this? Heard a few public health people quoted saying it wasn't necessary or that it would be harmful.
Probably an unrepresentative minority, but they seem to get a lot of airtime.
nejm.org/doi/full/10.10…
But actually it was masks the OP was complaining about: "there is a time and place for them".

Right, like now?
Read 4 tweets
21 Oct
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
Read 15 tweets
19 Oct
Turns out there were 2 studies last week comparing J&J + J&J booster to J&J + Pfizer booster! One was NIH, as most know. The other is from Singapore and it looks like a solid study too.

Most interesting: they looked at T cells too, not just antibodies!

medrxiv.org/content/10.110…
We see again that J&J+Pfizer gave higher antibody levels and neutralizing activity than J&J+J&J, and similar to Pfizer+Pfizer. Note wide range of interdose intervals (43-71d for J&J+J&J, 11-180d for J&J+Pfizer) but Ab levels actually quite tight.
While antibodies are the first line of defense and what block you getting infected, it's essential to have T cells for avoiding late complicatinos. It's widely proposed that the Ad vaccine of J&J may elicit more T cells.
Read 13 tweets
19 Oct
🎉🎇🙂 Wonderful news! @US_FDA will allow mix & match boosters!

As the linked article below says, booster freedom helps local health officials. And it's also the right thing scientifically, especially for #JnJers

This is the happiest I've ever felt from a FDA decision!
I had some hope FDA might do this, after Dr. Marks' said in Friday's VRBPAC meeting that they'd like to know what info was needed to approve mixed boosters, and some VRBPAC members replied that the "Mix and Match Booster Trial" results were clear enough

nytimes.com/2021/10/16/us/…
I'd learned from repeated lack of action not to hope too much. Gathering info on the benefits of heterologous boosts for #JnJers and seeing it tossed aside for various nonreasons made me feel like Sisyphus rolling a stone

So this news is like Sisyphus finally cresting the hill
Read 24 tweets

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