Thread by @MonicaGandhi9

NU VARIANT (B.1.1.529) in South Africa & why unlikely to evade vaccine-induced immunity. So, what is this variant? Number 1, we don't know yet if it is more transmissible. Still being studied & described. 59 cases uploaded to database
thenationalnews.com/coronavirus/20…

Okay, so what is a "variant" mean for COVID? Means mutations in spike protein that attaches the virus to the host cell: mutations that differ from the "ancestral strain". This is the bit of the virus that tends to mutate most (like H and N surface proteins of influenza). Also,

of the 8 vaccines approved by the WHO (Novavax will be added soon & will make the 9th), 6 of those 9 involve the spike protein in some way (either code for it with mRNA, DNA; Novavax is protein itself); 3 of the 9 are whole inactivated virions (Covaxin, Sinopharm, Sinovac)

The other major variants of concern (alpha, beta, gamma, delta) have 11-13 mutations across the spike protein, this B.1.1.529 one (which may be named nu) has 30 so more mutations than previous. However, the spike protein vaccines produce in-breadth T cells & polyclonal antibodies

Natural immunity & the whole inactivated viral vaccines like Covaxin allow immune system to see entire virus but spike protein vaccines also produce a complicated antibody response (called "polyclonal", not just along one spot) AND B/T cell responses.
sciencedirect.com/science/articl…

We have already discussed cellular immunity & how we know the vaccines produce B cells in germinal centers (proven by taking biopsies of lymph nodes). This paper posted shows us these B cells produce different antibodies including one called the "public" 2C08 antibody which

targets the end of the spike protein and where it binds to the host cell (called the receptor binding protein) and blocks infection by circulating SARS-CoV-2 and emerging variants of concern (because they will emerge without #globalvaxequity) both in vitro and in vivo. B cells

don't stuff themselves with antibodies & sit there- they PRODUCE antibodies directed against the variant they see in front of them (if see virus in future) because B cells "recipe book", "blueprint" to produce variant-directed antibodies, amazing paper:
science.org/doi/10.1126/sc…

Although will have to rely on B cells generated by vaccine (or natural immunity) to produce and adapt these antibodies (as booster will generate antibodies against ancestral spike protein) in response to new variant. And what about T cells? Nice paper from S. Africa showed us

that the AztraZeneca vaccine produced 87 T cells across spike protein: "vaccine caused expansion of CD4+/ CD8+ T lymphocytes to specific epitopes of the spike protein. Of 87 spike-specific antigens sequenced, 75 remained unaffected by" [beta variant]
nejm.org/doi/full/10.10…

So, there are 87 T cells at least across spike protein generated by the vaccine (this is an DNA/adenovirus vaccine) so if even 30 knocked out by mutations, still have in-breadth T cell response left. Try to explain how complex T cell immunity is here

https://twitter.com/MonicaGandhi9/status/1446901679308226560

And this is a thread to explain how B cells generated by vaccines or natural immunity will produce antibodies directed against the variants they see in the future if exposed to a new one (of any Greek alphabet designation)

https://mobile.twitter.com/monicagandhi9/status/1443016556460470272?s=10

AND THIS IS KEY: if vax'd or immune (even older produce B cells & T cells; immunocompromised have redundancy too), variant can't "set up shop" but can spread through population with less immunity (S Africa 21.3% vax'd). GLOBAL VAX EQUITY KEY - moral & protects against variants

And here is cellular immunity thread to explain bit more about complexity of immune system including immune memory- but we are simply NOT giving access to the vaccine worldwide & that is wrong (WHO is right; boosters for rich, no 1st doses for many)

https://twitter.com/monicagandhi9/status/1424174473402408960?lang=en

And finally, someone asked me if antiviral therapies still work against variants- yes, they are not directed against spike proteins- they are directed against enzymes in the viral lifecycle that enable the virus to replicate. Molnupiravir and Paxlovid

https://twitter.com/MonicaGandhi9/status/1456784050551619586

1 more point- here health minister said some of the variant cases detected in people's noses who were fully vaccinated but needed to test for travel. If you are well & fully vaccinated with a variant, that implies the vaccines actually work against it.
nytimes.com/2021/11/25/wor…