Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies

Allison J. Greaney, Tyler N. Starr, Christopher O. Barnes, Yiska Weisblum, Fabian Schmidt, Marina Caskey, Christian Gaebler, Alice Cho, Marianna Agudelo, Shlomo Finkin, Zijun Wang, Daniel Poston, Frauke Muecksch, Theodora Hatziioannou, Paul D. Bieniasz, Davide F. Robbiani, Michel C. Nussenzweig, Pamela J. Bjorkman and Jesse D. Bloom ()
Additional contact information
Allison J. Greaney: Fred Hutchinson Cancer Research Center
Tyler N. Starr: Fred Hutchinson Cancer Research Center
Christopher O. Barnes: California Institute of Technology
Yiska Weisblum: The Rockefeller University
Fabian Schmidt: The Rockefeller University
Marina Caskey: The Rockefeller University
Christian Gaebler: The Rockefeller University
Alice Cho: The Rockefeller University
Marianna Agudelo: The Rockefeller University
Shlomo Finkin: The Rockefeller University
Zijun Wang: The Rockefeller University
Daniel Poston: The Rockefeller University
Frauke Muecksch: The Rockefeller University
Theodora Hatziioannou: The Rockefeller University
Paul D. Bieniasz: Howard Hughes Medical Institute
Davide F. Robbiani: The Rockefeller University
Michel C. Nussenzweig: Howard Hughes Medical Institute
Pamela J. Bjorkman: California Institute of Technology
Jesse D. Bloom: Fred Hutchinson Cancer Research Center

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract Monoclonal antibodies targeting a variety of epitopes have been isolated from individuals previously infected with SARS-CoV-2, but the relative contributions of these different antibody classes to the polyclonal response remains unclear. Here we use a yeast-display system to map all mutations to the viral spike receptor-binding domain (RBD) that escape binding by representatives of three potently neutralizing classes of anti-RBD antibodies with high-resolution structures. We compare the antibody-escape maps to similar maps for convalescent polyclonal plasmas, including plasmas from individuals from whom some of the antibodies were isolated. While the binding of polyclonal plasma antibodies are affected by mutations across multiple RBD epitopes, the plasma-escape maps most resemble those of a single class of antibodies that target an epitope on the RBD that includes site E484. Therefore, although the human immune system can produce antibodies that target diverse RBD epitopes, in practice the polyclonal response to infection is skewed towards a single class of antibodies targeting an epitope that is already undergoing rapid evolution.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24435-8

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DOI: 10.1038/s41467-021-24435-8

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