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
By Fabian Schmidt, @FraukeMuecksch, Yiska Weisblum, Justin Da Silva, Eva Bednarski, Alice Cho @VinciZijun, @c_gaebler @marinacaskey
Link to full manuscript:…
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
Longitudinal analyses of plasma from convalescent individuals (1m, 6m, 12m after infection) shows substantial Omicron neutralization escape
Longitudinal analyses of plasma from individuals who were vaccinated only (2x mRNA or 1x J&J) shows substantial Omicron escape
KEY POINT: Increasing immunity with an mRNA booster shot on top of prior infection or prior 2x mRNA vaccination confers 30x to 200x higher neutralization titers vs Omicron or PMS20
It is time to discard the notion that two doses of mRNA means “fully vaccinated”
It is time to discard the notion that prior SARS-CoV-2 infection means you don’t need to be vaccinated.
The @medrxivpreprint version of this work is out today…

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More from @PaulBieniasz

20 Sep
Our paper on #polymutant SARS-CoV-2 spikes (led by Fabian Schmidt and Yiska Weisblum with @theodora_nyc and @NussenzweigL) now published in @Nature…
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
Read 5 tweets
20 Jan
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.…
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
Read 8 tweets

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