Thread by @PaulBieniasz

Our new preprint with @NussenzweigL @theodora_nyc and @bjorkmanlab

K417N, E484K and N501Y in SARS-CoV-2 “variants of concern” in UK, SA and Brazil are antibody escape mutations.
biorxiv.org/content/10.110…

Each confers resistance to commonly elicited RBD neutralizing antibodies cloned from mRNA vaccinees
Together, K417N, E484K and N501Y confer some (not complete) resistance to neutralization by vaccine recipient polyclonal plasma.

If we grow rVSV/SARS-CoV-2 with the cloned antibodies, most select for mutations at K417, E484 and/or N501.

Structures of vaccine-recipient antibodies with spike show K417, E484 or N501 are often in the epitopes of RBD-specific, vaccine elicited neutralizing antibodies

Importantly, near-identical anti-RBD antibodies are elicited in naturally infected or vaccinated individuals. Together, these data suggest that the emergence of K417N/T, E484K and N501Y mutations represent the beginnings of SARS-CoV-2 antigenic drift, as host immunity accumulates

The vaccines will in all likelihood still work well against the variants, but this isn’t the time (in my view) to be doing population-wide experiments with vaccine regimes which delay the boost (2nd dose) that is all important for maximizing plasma neutralizing potency

If we grow rVSV/SARS-CoV-2 with the cloned antibodies, most select for mutations at K417, E484 and/or N501.

Structures of vaccine-recipient antibodies with spike show K417, E484 or N501 are often in the epitopes of RBD-specific, vaccine elicited neutralizing antibodies

Notable contributors include: @VinciZijun Fabian Schmidt Yiska Weisblum @FraukeMuecksch @cobarnes27 @FinkinS1 @Doctor_DSB @c_gaebler Melissa Cipolla Jenna Lieberman Rafael Cassellas and many others. Team effort

More detailed thread from @VinciZijun (with figures/data)

https://twitter.com/VinciZijun/status/1351707342061129729?s=20