Jesse Bloom PRO
Scientist studying evolution of proteins and viruses.
These slides at https://slides.com/jbloom/covid-19-clinical-antibodies
"... novel spike mutants rapidly appeared after in vitro passaging in the presence of individual antibodies..."
From the paper describing REGN-CoV2 cocktail
RBD
fluorescent antibody
fluorescent tag on RBD
In maps, tall letters indicate strong escape mutations
Sort done at single antibody concentration, which determines sensitivity!
Tall letters = strongly escape binding. For instance, mutations at 446 escape, but those at 484 don't. However, quantitative relationship of letter height to IC50 depends on FACS gate: we confidently capture mutations with >100 fold effects, but can miss smaller ones.
Image shows key sites of interest, click here for interactive map of all mutations.
Note: these are high-throughput maps generated using yeast display. We have found excellent correlation between the maps and pseudotyped viral neutralization assays (see papers above), but still recommend validating key conclusions.
Patient described in Choi, Choudhary, ...,. Cernadas, Li. New England J Medicine (2020)
Note extensive genetic hitchhiking and competition among viral lineages; also described in within-patient evolution of influenza in persistent infections: Xue et al, eLife (2017)
Importantly, our complete maps show that four of these mutations reduce binding by one or the other of the REGN-COV2 antibodies, only one of which was identified by Regeneron's escape selections. Illustrates value of complete maps.
Studies validating these conclusions from the mapping:
Crowe lab (Vanderbilt):
Bloom lab (Fred Hutch)
Tyler Starr
Allie Greaney
Adam Dingens
Amin Addetia
Will Hannon
These slides at https://slides.com/jbloom/covid-19-clinical-antibodies
Li lab (Brigham & Women's):
By Jesse Bloom
Viral mutations and antibodies used to treat COVID-19
Scientist studying evolution of proteins and viruses.