Here's how mutations in #SARSCoV2 Nu variant (B.1.1.529) will affect polyclonal and monoclonal antibodies targeting RBD. These assessments based on deep-mutational scanning experiments; underlying data can be explored interactively at https://jbloomlab.github.io/SARS2_RBD_Ab_escape_maps/ … (1/n)
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But I'd expect the Nu variant to cause more of a hit on vaccine- and infection-elicited antibody neutralization than anything we've seen so far. (6/n)
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We can also look at some key monoclonal antibodies. the REGEN-COV cocktail is likely to take a hit for the Nu variant, especially the REGN10987 component. (7/n)pic.twitter.com/iZYGxNZl2o
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The early Eli Lily antibodies like LY-CoV555 (bamlanivimab) and LY-CoV016, which were already in trouble with current variants, aren't going to do any better against the Nu variant. (8/n)pic.twitter.com/My8GMUDdLa
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However, it appears the AstraZeneca AZD7442 cocktail and Vir's S309 are likely to hold up better against the Nu variant. See below. (9/n)pic.twitter.com/PNlJjHc5fT
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You can explore other antibodies that might be of interest to you at https://jbloomlab.github.io/SARS2_RBD_Ab_escape_maps/ …. Importantly, all above results from high-throughput deep mutational scanning, and need to be validated in traditional experiments for high confidence. (10/n)
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Also note large antigenic change does not mean Nu will necessarily spread & outcompete other variants. That will also depend on its transmissibility, which has been discussed by
@Tuliodna & others (eg, https://twitter.com/Tuliodna/status/1463911571176968194 …) and for which data remains preliminary. (11/n)
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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)Show this thread -
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)
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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)
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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)
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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)
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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 …).Show this thread -
And probably I should have used the variant name B.1.1.529 throughout above thread...https://twitter.com/theosanderson/status/1464007031174619143 …
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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 …
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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 …
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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 …Show this thread -
Here are data from one of
@AllieGreaney's papers (Fig 5 of https://www.science.org/doi/10.1126/scitranslmed.abi9915 …) showing that a K417-G446-E484 triple mutant sometimes but not always fully escapes neutralization by RBD-targeted antibodies, and effect is worse for convalescent than mRNA-1273 vaccine sera.pic.twitter.com/rtdbwS7QQ7
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Also adding this as another highly informed view just for balance on question of possible extent of antibody neutralization escape:https://twitter.com/theodora_nyc/status/1464257411582148608 …
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