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Prof. Shane Crotty Profile picture
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2 Nov, 6 tweets, 2 min read
This week’s Crotty lab Journal Club, quite a surprising paper:
"Early developing B cells undergo negative selection by central nervous system-specific antigens in the meninges” 
Selected by postdoc Zeli Zhang 🧵
@ImmunityCP
sciencedirect.com/science/articl…
The authors identified early B cell development in the meningeal of mice and non-human primates, which was quite surprising. Image
Meningeal developing B cells were replenished from hematopoietic stem cell (HSC)-derived progenitors. Image
Autoreactive immature B cells that recognized MOG, a central nervous system-specific antigen, were eliminated specifically from the meningeal. Image
These interesting data demonstrate that the meninges function as a distinct reservoir for B cell development, allowing negative selection of CNS-antigen-autoreactive B cells.
Overall, a wonderful paper. But it was missing a photo of the lead mouse helmets!

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More from @profshanecrotty

Prof. Shane Crotty Profile picture
29 Oct
What COVID vaccine would I give my kid?
If I had a kid age 5-11, I would get them the Pfizer vaccine, ASAP.
Even if the Moderna vax were available, I would go with the Pfizer vax for my kids. Because the Pfizer vaccine is a 10mcg dose. 🧵
10mcg Pfizer gave great immune responses in 5-11 year olds in the Phase 2/3 clinical trial, as good as 30mcg in 20 year olds ( equal antibody levels & ~100% antibody positive). Great to see the kids COVID-19 vaccine results from Pfizer provided to the FDA.
Given that kids generally have a much milder course of COVID-19 disease, having a level of immunity equal to that of young adults (or somewhat less than young adults that got the Moderna vaccine) should be more than enough for a 5-11 year old.
Read 14 tweets
Prof. Shane Crotty Profile picture
25 Oct
What should I get as the 2nd dose? That's a question I get a lot.

If it were me, and I had only gotten 1-dose of vaccine & was soon to get my 2nd dose, here's what I would do:
1st dose + 2nd dose
J&J + Mod
Pfizer + Mod
Mod + Mod
See a pattern? 🙂 Moderna 2nd gives the most robust immune response with any of the others. But Pfizer is pretty close! (and I'd get 100mcg Moderna if I could)
Both in the Atmar/Lyke et al. work, and multiple published studies of AZ vax + RNA 2nd, getting RNA vaccine as the 2nd dose after an adeno vector has resulted in better antibody and T cell responses, compared to 2 doses of adeno.
Read 6 tweets
Prof. Shane Crotty Profile picture
25 Oct
1-dose J&J is ok for a while, but needs a 2nd dose of vaccine (any) by 6 months. Anytime after 2 months is fine. A short thread on the recent J&J data to the FDA . 🧵
fda.gov/advisory-commi…
J&J 1-dose clinical trial efficacy.
These data, from a placebo controlled clinical trial for efficacy + safety, are robust. They are also consistent w/ multiple "real world" studies. Efficacy v. cases, hospitalizations, and deaths isn't as good as mRNA vaccines, across 6 months.
Or graphically:
Read 8 tweets
Prof. Shane Crotty Profile picture
25 Oct
Is it good to mix COVID vaccines?

This is a really great clinical study by Lyke et al., reported at the recent FDA meeting.

Mix-and-match COVID vaccines

fda.gov/advisory-commi…
Mix-and-match COVID vaccines
Key findings:
🔵   mRNA + mRNA combinations are similar
🔵   J&J + mRNA gives much higher antibodies than J&J + J&J
🔵   No T cell data (sigh)
All the key data:
Read 11 tweets
Prof. Shane Crotty Profile picture
19 Oct
Why isn't there a Delta variant vaccine?

I hear this a lot. 🧵 Three reasons:
1. The regular vaccines give great booster responses against Delta and other variants.
2. “Original recipe’ vaccine is better suited for other variants
3. It is faster to proceed with original vaccines
1/ The regular vaccines give great booster responses against Delta and other variants
This was first shown by Moderna, with 'original recipe' vaccine booster, compare to Beta booster.
nature.com/articles/s4159…
And for T cells, the T cell epitopes between variants are highly conserved, so the 'original recipe' vaccine should be a good booster. Though no T cell booster data are published.
doi.org/10.1016/j.xcrm…
Read 6 tweets
Prof. Shane Crotty Profile picture
19 Oct
FDA panel greenlighted Moderna booster vaccines. CDC will consider it this week. My thoughts 🧵:
🔵   Moderna booster definitely enhances immunity
🔵   Moderna boosters for people > 65 at 6+ months is reasonable, and healthcare workers
🔵   Moderna booster needed less than Pfizer
🔵   The Moderna booster definitely enhances immunity
Over the Moderna booster data and FDA filing look good. The data are more limited than desired, but it all makes sense.
The FDA probably struggled with the idea of making a Moderna booster recommendation different than the Pfizer booster recommendation they recently made.
Read 18 tweets

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