Why should we not worry about VARIANTS "escaping" immunity from vaccines or natural infection; why are we not likely to need vaccine BOOSTERS? Remember immunity is both antibody and cell-mediated (CD4 and CD8 cells). Long-term immunity mediated by memory B & T cells (both get
stimulated if they see the virus again). We now feel secure that T-cell immunity will be preserved against variants after these 2 papers reassured us. Sette's great paper showing T-cell immunity after natural infection or mRNA vaccination preserved against biorxiv.org/content/10.110…
B.1.1.7 (UK), B.1.351 (South Africa), P.1 (Brazil), and CAL.20C (California). Means T cells generated by vaccines can readily fight these variants. 2nd paper is by Dr. Redd one showing that CD8 responses preserved despite spike protein mutations
academic.oup.com/ofid/advance-a…
in B.1.1.7 (UK), B.1.351 (S. Africa), P.1 (Brazil);Basically, your T cell response is so complicated & varied across the spike protein, a few mutations don't matter. Could be true of antibodies too; we just only measure a few (remember that); T cells assays in labs reveal breadth
I tweeted 3rd paper that showed this back in Feb. This was written at a time UK was worried about vax not working against B.1.1.7 and B.1.351. After vaccine, "the majority of the T cell response was directed against epitopes conserved" across variants.
researchsquare.com/article/rs-226…
"However, after single vaccination, which induced only modestly neutralizing homotypic antibody titers neutralization against the variants of concern was completely abrogated in the majority of vaccinees". So, T cells after vax neutralize variants. 4th paper that showed this next
And T cells generated by AZ vaccine: "of 87 spike-specific antigens [T cell epitopes] identified by the sequencing, 75 remained unaffected by the B.1.351 mutations" (South Africa) variants in the South Africa trial
nejm.org/doi/full/10.10…
And finally, this large 6-month analysis of the real-world effectiveness of the Pfizer vaccine across multiple settings shows high effectiveness against the B.1.351 (E484K containing, S. Africa) variant. Will we need boosters? Likely not- continue tomorrow
pfizer.com/news/press-rel…
But this very famous long-time virologist Dr. Vincent Racaniello was a bit more forceful than I just was when he said- please stop with the variants!
thestreet.com/latest-news/th…
Wanted to add to this thread on how vaccines cover variants (see above, T cells) to explain why we are unlikely to need yearly boosters. #1 - vaccines cover variants. As cases come down, less chance virus to mutate; #2- coronavirus doesn't mutate readily
nature.com/articles/nrmic…
Coronaviruses actually have a strong "proofreading" mechanism, meaning they don't tolerate mutations and go back and fix them unlike influenza (another RNA virus with a very "leaky" or mutation-prone polymerase or replicating mechanism); #3 - we should have long-lasting immunity
Remember my ode to memory B cells when I cheated on T cells and told you about them. We know that memory B cells generated by these vaccines because these researchers actually biopsied lymph nodes of brave volunteers to prove it! And we know memory B
researchsquare.com/article/rs-310…
cells can trigger immune responses DECADES later if see virus again. So, don't think we are going to be needing yearly booster shots for #covid19. And probably need better global flu vaccine too. Hope this thread relieves some tension on variants/boosters
nature.com/articles/natur…
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