Thread by @DrEricDing

GOOD NEWS—a mutation seen in a few #SARSCoV2 variants doesn’t seem to harm the Pfizer/BioNTech vaccine, finding “no reduction in neutralization activity against virus”.

HOWEVER—did not yet test for worrisome E484K mutation, which many experts say might.🧵
statnews.com/2021/01/08/pfi…

2) A colleague of mine, @AliNouriPhD, wrote a post on a recent reinfection case involving the E484K mutation. We know it can “escape” many current neutralizing antibodies.

https://twitter.com/AliNouriPhD/status/1347016588579508224

3) What do we mean by “escape neutralizing antibodies”? It means antibodies known to bind the common type of the #SARSCoV2 virus no longer bind to the mutated version. And that is what we are noticing with the E484K mutation that’s in receptor binding domain. (@jbloom_lab credit)

4) that said, within the same person, this fraction that escape antibodies also changes over time. On day 18, there was a lot of escape, but on day 94, much less. Hence lots of uncertainty about vaccine or MAB drugs long term.

5) That said, BioNTech founder says it only takes them 6 weeks to synthesize a new mRNA vaccine for any new variant. Tricky question is how much clinical testing needs repeated / how long before it can be deployed. Another 10 months w/ Phase 3 mega trial again? Or shorter P1&2?

6) But the E484K can cause large 10x or more reductions in neutralization in some. (Wildtype= common #SARSCoV2). That is a huge huge reduction.

7) To be clear—“neutralization” = stopping the virus. So the E484K showing a 10x reduction of neutralization of the virus by various antibodies compared to wildtype (common #SARSCoV2) is a very bad thing. It means the virus with E484K is worrying for “immune escape”

https://twitter.com/jbloom_lab/status/1346442000472580098

8) And so which #SARSCoV2 strain has the E484K mutation? The South Africa 🇿🇦 variant - aka 501.V2 or the B.1.351 lineage variant. This is why we are worried about that B1351 variant so much for vaccine escape potential.

https://twitter.com/jbloom_lab/status/1346442016092082176

9) To be clear, many variants have the E484K, but most famous is SA found B1351 which has many mutations. SA variant also has the N501Y mutation tested to bind ACE2 more strongly and more infectious, but that N501Y doesn’t escape antibodies or the Pfizer vaccine (first post).

10) and the @jbloom_lab study found another mutation of concern— at the F456 of the spike protein’s receptor binding domain. (This one not part of SA 🇿🇦 B1351 or UK 🇬🇧 B117). Let’s hope this mutation doesn’t proliferate.