Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies
- PMID: 34234131
- PMCID: PMC8263750
- DOI: 10.1038/s41467-021-24435-8
Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies
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.
Conflict of interest statement
Subsequent to completion and submission of the initial version of this study, J.D.B. began consulting for Moderna on viral evolution and epidemiology. J.D.B. has the potential to receive a share of IP revenue as an inventor on a Fred Hutch optioned technology/patent (application WO2020006494) related to deep mutational scanning of viral proteins. The Rockefeller University has filed a provisional patent application related to SARS-CoV-2 monoclonal antibodies on which D.F.R. and M.C.N. are inventors. The Rockefeller University has applied for a patent relating to the replication-competent VSV/SARS-CoV-2 chimeric virus on which Y.W, F.S., T.H. and P.B. are inventors (US patent 63/036,124). The remaining authors declare no competing interests.
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Update of
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Mutational escape from the polyclonal antibody response to SARS-CoV-2 infection is largely shaped by a single class of antibodies.bioRxiv [Preprint]. 2021 Mar 18:2021.03.17.435863. doi: 10.1101/2021.03.17.435863. bioRxiv. 2021. Update in: Nat Commun. 2021 Jul 7;12(1):4196. doi: 10.1038/s41467-021-24435-8. PMID: 33758856 Free PMC article. Updated. Preprint.
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