Our new paper is out showing T cell responses to the Novavax vaccine, studying Novavax vaccine clinical trial participants, led by the outstanding Dr. @CModerbacher! With a nice commentary article by @PC_immuno . 🧵

jci.org/articles/view/…

jci.org/articles/view/… This complements our immune memory study comparing 4 COVID vaccines, including Novavax.

https://twitter.com/erictopol/status/1529834331127943168

Our paper on immunization and long germinal centers is out in @Nature! Congrats to the indefatigable and brilliant JH Lee and @harrysutton93 ! 🧵
nature.com/articles/s4158…

And Free link: rdcu.be/cV2xv We put together an extensive tweetorial of this study earlier:

https://twitter.com/profshanecrotty/status/1473673803263668224?s=21

The brand newly approved COVID boosters are going to work well. They won’t be a game changer—won’t prevent all infections—but are the best booster option and will provide a lot of protection.

It’s the immunity you want heading into the Fall and winter.

nytimes.com/2022/08/31/wel… To clarify a few things and add some details:

The Omicron booster vaxs are clearly safe. Billions of Covid mRNA vax doses have been given, with excellent safety. Regarding the new “bivalent” boosters, there was a 2021 bivalent COVID booster vax human trial…

Wonderful workshop on Vaccine Durability questions today and yesterday with NIAID. Thanks to my session co-chair @TheBcellArtist, and the awesome panelists. There was intensive and wonderful discussion, and we did make several recommendations 👇🏼 The awesome panelists were @deeptabhattacha @KingLabIPD, Rama Amara, Kanta Subbarao, and Chris Chiu (are they on Twitter?)

The rapid fire recommendations at the end of the discussion:

It is good to see Novavax antibody data on Omicron 1,2,4 and 5 from @veeslerlab out. science.org/doi/10.1126/sc… We provided the 2x Novavax immunized donor samples, which we extensively compared to mRNA and J&J vaccines for immune memory antibodies, CD4 T cells, CD8 T cells, and memory B cells in a recent paper sciencedirect.com/science/articl…

What parts of the immune system are protecting you against COVID? Immunology is complicated, so here's a graphic to try and explain it.
Layered defenses against SARS-CoV-2, or the “Swiss cheese” model of immunity. Multiple types of adaptive immunity with diverse mechanisms likely provide layers of defense against COVID-19. Conceptually, these are like a “Swiss cheese model”: even though each layer is imperfect, together they keep the pathogen from breaching all layers of defense.

Crotty lab journal club by @P1RAD:
Here is an immunological reason to resist raw cookie dough: Salmonella infection can induce monocytes that disrupt pre-existing germinal center (GC) responses to a primary infection (or potentially vaccines) 🧵[1/5]
cell.com/immunity/fullt… Work @ImmunityCP by @AdiBiram, @ZivShulman & colleagues show in a mouse model of Salmonella infection that infiltration of IFNɣ-induced monocytes (CCR2+ Sca1+ Ly6C-hi) from the bone marrow to peripheral lymphoid organs suppress GC B cells [2/5]

Our new pre-print posted. We compare immune memory to Moderna, Pfizer, J&J, and Novavax COVID-19 vaccines head-to-head. T cells, B cells, and antibody. We think this is the most comprehensive immunological evaluation of these four different vaccines. 1/17
biorxiv.org/content/10.110… These comparisons are of broader interest, because they compare human acute and memory immune responses longitudinally to three different vaccine platforms: mRNA, viral vector, and protein. 2/17

What comes after Omicron? A thorough article with thoughtful comments by @EJohnWherry @deeptabhattacha. I talk about immunity, misconceptions about disease severity, and virology. And my coffee mug analogy about how brilliant your immune system is! 🧵1/4

buzzfeednews.com/article/danver… Your immune system has really been brilliant at recognizing COVID vaccines & evolving immune responses that not only recognize the Spike in the vaccine, but also made educated guesses about what variants may look like—even though your immune system didn’t get to see any variants!

1st thread on our long germinal center (GC) preprint was last week. I promised a 2nd to dive into more of the biology:
Do naive B cells sustain long GCs?
Do GC cells have clonal migration to other lymph nodes during an ongoing GC?
Do low affinity B cells compete in these GCs? 🧵 If you missed the 1st thread, it's here:

https://twitter.com/profshanecrotty/status/1473673803263668224?s=21

Our newest study reveals some surprising immunology, which is relevant for vaccines.
We immunized animals with a protein vax and waited to see how long germinal centers (GC) would last. Expectations were GCs would peak by 3 weeks & be gone by 6. How long did they actually last?🧵 A LOOOOONG time!

Vaccine-binding GC cells PEAKED 10 weeks after immunization.

So we waited....

biorxiv.org/content/10.110…

3 studies today on antibodies & Omicron.
🔵 There may be a large drop in neutralization of Omicron
🔵 Antibodies stop Omicron well in hybrid immunity (infected+vax)
🔵 Sotrovimab is active versus Omicron

Take home: Get vaccinated. Get boosted. Immune system is clever. 🧵 1/n Live virus neutralization preliminary data from @Sigallab in South Africa found a 41x drop in vax neutralization of Omicron. That is a large drop. Seeing hybrid immunity do much better is encouraging. Average Omicron neutralization of ~1,000 was good (>vax neut of WT). 2/n

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.

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.

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)

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.

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)

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…

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.

CDC Director Dr. Walensky made the right decision last night on boosters. 🧵
Boosters now available (not required) for Pfizer vaxxed after 6 months:
🔵  65 and older
🔵  healthcare workers
🔵  nursing home residents
🔵  50 and older with health problems
apnews.com/article/corona… This was in line with the FDA decision last week. It also matches my suggestions two weeks ago on TWIV and VOSD. And earlier on UCSF Grand Rounds. It makes sense to have vaccine boosters available to these people, who received the Pfizer vaccine.

Good news! Pfizer data today indicate they have a safe and effective COVID-19 vaccine for kids ages 5 to 11. Kids vaxxed by Halloween? 🧵
🔵  Antibody titers as high as adults
🔵  "Favorable safety profile" with 10 microgram dose used
🔵  Filing with FDA

pfizer.com/news/press-rel… 🔵  Antibody titers were as high as adults

The fact that the peak antibody titers are equal between the kids 5 to 11 years old and young adults indicates the COVID vaccine will be protective in the kids.