Bloom Lab

As @trvrb discussed in excellent recent thread, selection on variants so far may be dominated more by transmissibility than antigenic selection (https://twitter.com/trvrb/status/1462816217794695170 …). But I'm not as sanguine that antigenic selection isn't also playing substantial role... (12/n)

Reason I say that is comparison of Nu variant to BANAL-20-52, a SARS-related CoV isolated from bats. If we compare both BANAL-20-52 and Nu to Wuhan-Hu-1, Nu has *many* more mutations that strongly affect antigenicity (https://twitter.com/jbloom_lab/status/1440309655087902720 …). (13/n)

If selection was mostly for transmissibility, I'd expect sites of divergence of Nu and BANAL-20-52 relative to Wuhan-Hu-1 to perhaps be similarly distributed with respect to antigenic sites. But instead, Nu mutations much more focused in major antigenic sites. (14/n)

We can also use deep mutational scanning to assess how mutations in Nu affect ACE2 affinity (https://twitter.com/jbloom_lab/status/1463879246875529224 …). But I suspect works less well than for antigenic mutations discussed above as there's lot more mutational epistasis for ACE2 affinity (eg, N501 & Q498). (15/n)

Important caveat: all of above is based on deep mutational scanning experiments. I'm sure more Nu-specific data will emerge in coming weeks to months. But I think it's useful to use prospective data we already have to calibrate what to expect. (16/n)

Thanks to @AllieGreaney @tylernstarr for doing deep mutational scanning on which above is predicated, & @NussenzweigL @VUMC_Vaccines @seth_zost @Vir_Biotech for sharing the antibodies. And of course the scientists providing rapid information about Nu (https://twitter.com/Tuliodna/status/1463911554538160130 …).

And probably I should have used the variant name B.1.1.529 throughout above thread...https://twitter.com/theosanderson/status/1464007031174619143 …

For people interested in G446 mutations, I'm going to link back to some details on this site. Here is an old thread discussing how G446 is a major site of escape in the class 3 epitope where (as of March 2021) mutations were not prevalent:https://twitter.com/jbloom_lab/status/1372669322657550337 …

Also, here are old data showing how for a minority of convalescent individuals, the epitope centered on G446 is immunodominant with respect to serum neutralization:https://twitter.com/jbloom_lab/status/1359136451875598345 …

Also, checkout the awesome CoV-RDB database of Bob Shafer, @Philip_Tzou, @sergeilkp, K Tao which compiles experimental data on G446 (and also whatever other mutation you care about): https://covdb.stanford.edu/search-drdb/?host=human&position=S%3A446 …