This study flew under the radar (only 1 news article): Omicron antibodies in participants of the NIH mix and match trial

Results: 3xRNA ~ 2xRNA+JJ ≥ JJ+RNA >> JJ+JJ

JJ+JJ ends up 10x worse than 3xRNA

medrxiv.org/content/10.110… @PaulSaxMD Image
Also confirms JJ is a poor booster for JJ, for either "original" D614G or Omicron. Image
Above, the JJ+Pfizer looked about 2x worse than 3xPfizer. Confidence intervals are wide, but another underreported Omicron study found JJ+Pfizer was ~3x worse than Mod+Mod+Pfizer. So this effect size seems consistent.

Great graphics BTW

medrxiv.org/content/10.110… Image
The difference between JJ+RNA and 3xRNA was bigger in the @BalazsLab study. I believe those patient samples may have been more heterogeneous. Regardless JJ+RNA is consistently lower than 3xRNA.

cell.com/cell/fulltext/… Image
Returning to the second paper by the de Vries lab, they also looked at B and T cell responses to original spike, over time after "full vax" (1xJJ or 2xAZ or 2xRNA)

No surprises: we see again that the 2-dose vaccines have higher Ab levels at 1mo than at 6mo.

Peak Mod>Pfiz>AZ>JJ Image
For those who might have just read press releases or news articles that reiterate press releases, yes JJ (Ad26COV2S) Ab levels go up and then stabilize between 2mo and 6mo. But the whole time it is below the levels of 2xRNA (mRNA or BNT), so there's no net advantage of 1xJJ.
How about T cells, which some people thought would be an advantage of adenovirus (Ad, vectored) vaccines? As measured by IFNgamma release, they're worse for 2xAZ (ChAdOx) or 1xJJ (Ad26COV2s) vs 2xRNA (mRNA1273).

White circles = selected for in-depth analysis Image
They also looked at unboosted Ab levels against Omicron. This is a measure of breadth of the response. You can see convalescent sera and Moderna had the most Omicron neutralization (look at #'s above), everything else similarly poor. Image
And they also looked at T cell responses across strains. Again Moderna much better than everything else. Little differences across strains (because T cell epitopes are from anywhere in the protein, and not subject to the same selective pressure) Image
So the de Vries study is remarkably consistent in showing Moderna to have the broadest B cell responses, and the strongest B and T cell responses. It does seem like the most protective of the vaccines, and Modernites also get to enjoy a 3rd shot of their choice (4 if they are IC)
And finally the de Vries study, like the Balazs study, is a joy to read because of the excellent graphics. Everything is consistently labelled, well organized, and color-coded, and there's a cartoon of the experimental process. You hardly ever have to look at the legend. 🙏👏👏

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More from @michaelzlin

Feb 3
Thank you @LauermanJohn for revealing the untold origin story for Pfizer's Paxlovid COVID-19 pill.

The interesting part: Merck's drug boceprevir provided an essential backbone structure for Paxlovid, and boceprevir is still under patent.

bloomberg.com/news/articles/…
The article reveals many things not publicly known earlier.

First, Merck had (like my own lab and others) found boceprevir to have some activity against SARSCoV2. Not too surprising, as boceprevir is a HCV protease inhibitor, and SARSCoV2 protease is homologous to HCV protease.
I had emailed Merck to let them know in case they didn't already. But I expected the to know, and this confirms it. They determined that is was unlikely to work well for COVID19 on its own, but Merck was in a good position to modify it to work better, but they didn't.
Read 4 tweets
Feb 2
A recent study by Novavax suggests it may be able to provide broader protection across variants than other vaccines so far. That has interesting implications for vaccine design, if true.

This seems to have escaped analysis entirely, so we'll take a look.

medrxiv.org/content/10.110…
The study came out on 12/25. It contains the data behind Novavax's 12/22 announcement that 3 shots of their vaccine provided Omicron protection. That got into the news, but nobody came back on Christmas to write about the actual findings (I wonder why).
ir.novavax.com/2021-12-22-Nov…
Sorry, Novavax, but you might benefit from hiring a science communication consultant for advice on publication strategy and writing. Besides the poor decision to release your article on 12/25, assuring no one will analyze it, the abstract is a disaster. Because there isn't one. Image
Read 23 tweets
Jan 31
🙄 Count on some "researchers" to claim the obvious answer isn't the answer.

Did we want a vax to the original strain? We did?

Is SARSCoV2 now mostly Omicron? It is?

Okay then...
Chances are nonzero that the next variant will come from the currently most widespread and most contagious variant, i.e. Omicron. Good to be prepared.
Basically in this epidemic, if the question is "should we .... just in case?" the answer is yes. Just do it.
Read 4 tweets
Jan 29
What's the diff between a chief librarian and a CDC director?

When a chief librarian leads his staff from a 1000mi away, it's a scandal.

When the CDC director does it during the deadliest pandemic ever, it's somehow not.

Yes, literally phoning it in.

seattletimes.com/entertainment/…
Well the director does fly in a few times a month. Is that enough time to see everything interesting from 10k staffers? Also doubt much reform/reorg is going to happen remotely

google.com/amp/s/time.com… Image
I expected the WH would had made willingness to move to Atlanta a precondition of appointment for the CDC director during our biggest loss of life ever, when access to info and good communication is more important than ever.
Read 8 tweets
Jan 25
If you haven't heard, FDA approved molnupiravir for COVID19. I've been concerned it could create highly mutated SARSCoV2 and make new enhanced viruses more likely. Today a new study supports the idea that letting viruses sample multiple mutations is risky.
It's already known that molnupiravir doesn't kill off all mutant viruses after 5 days, but does introduce mutations into the viral genome. That is after all its only mechanism of action. Some of the mutated viable viruses may then hop to other people.
The pro-MOV argument is that MOV drops levels of viable virus more than it increases mutations in the remaining viruses, which might mean fewer later mutational templates. For several reasons, these arguments are not convincing, which means we're making an unusually dangerous bet
Read 18 tweets
Jan 24
New CDC studies have good news for the boosted, I mean up-to-date, bad news for double-jabbed only

The good news: Protection from Omicron ER visits is 82% for the up-to-date

The bad news: Protection down to measly 38% for non-boosted 6mo after dose 2

cdc.gov/mmwr/volumes/7…
First a quick detour: We're now calling people who are adhering to the most recent recommendation up-to-date on their shots. I think this is a good thing. Unlike "fully vaxxed" it is language that can be continually used even as guidance changes.
usnews.com/news/health-ne…
Now back to the studies. The first one, linked in the top post, looked at ER/urgent-care visits, and at hospitalizations. Hospitalization protection against Omicron is also poor after two doses and waning. It's also restored to excellent levels by a third dose.
Read 20 tweets

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