Not the first, but a quite comprehensive analyses of Omicron neutralization resistance with @theodora_nyc, @NussenzweigL
Bottom line is fairly consistent with other mini-studies out this week, some quantitative discrepancies between groups
We compared Omicron to an antibody resistant spike (PMS20) that we previously designed. Omicron distribution of changes and neutralization properties are similar to PMS20. Suggests that antibody evolutionary pressure drove Omicron emergence
It shows that plasma antibodies target numerous epitopes in SARS-CoV-2 spike such that ~TWENTY mutations are needed for neutralization escape from polyclonal antibodies elicited by infection or vaccination.
Notably, antibodies from those who had been BOTH infected AND later vaccinated (2x mRNA), neutralized the #polymutant and as well as diverse bat/pangolin sarbecoviruses and SARS-CoV
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