Thread by @AllieGreaney

Excited to share this preprint biorxiv.org/content/10.110… in collaboration with @sigallab @khadijakhan24 at @AHRI_News and @tylernstarr @eguia_rachel (and many others). @jbloom_lab says it best; see 🧵👇. To add... (1/10)

https://twitter.com/jbloom_lab/status/1448495744453726208

We’ve known for months nature.com/articles/s4158… nature.com/articles/s4158… nature.com/articles/s4159… that #SARSCoV2 Beta (B.1.351) has less susceptibility to antibody binding and neutralization. But does Beta influence the antibodies that are elicited by infection? (2/10)

We saw evidence that there was something different about the antibody response elicited by this variant from @sigallab, @Tuliodna & Penny Moore nature.com/articles/s4158… nejm.org/doi/full/10.10… (3/10)

We look into this question further by identifying mutations that reduce binding and neutralization of convalescent plasmas from individuals infected with the Beta variant. (4/10)

Beta has the E484K mutation to immunodominant site 484, and the antibody response is understandably shifted. To our surprise, mutations to 484 still strongly reduced antibody binding. But, the K484E reversion had little effect on neutralization. (5/10)

There was a modest shift towards antibody targeting of the class 3 epitope, which is conserved between early 2020 and Beta viruses. (6/10)

Interestingly, work from @sigallab @Sandile_Cele22 and others (sciencedirect.com/science/articl… medrxiv.org/content/10.110… ) has found that Beta-elicited plasmas are less effective at neutralizing the Delta variant than early 2020 plasmas. (7/10)

The Delta variant has the RBD mutation L452R (and T478K), conserved between the early 2020 viruses and Beta (and which is in the class 3 epitope targeted by Beta plasmas). (8/10)

Delta (*not* Beta!) seems likely to fix and SARS-CoV-2 will continue to evolve. Individuals will acquire increasingly diverse & complex infection/vax hx. We must continually evaluate sites under immune selection and the antigenic effects of the virus’ ongoing evolution. (9/10)

Thanks to our collaborators: @farinakarim @Sandile_Cele22 @HelenChuMD @veeslerlab @johnbowenbio @DavideCorti6, Andrea Loes, and Jenny Logue. (10/10)

And, a recent preprint from @MomsenReincke

https://twitter.com/MomsenReincke/status/1448690452102844417?s=20

suggests that the mechanism underlying this shift in immunodominance could be due in part to differential utilization of germline antibody genes with D614G vs. Beta infection!