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

TitleMapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies.
Publication TypeJournal Article
Year of Publication2021
AuthorsGreaney AJ, Starr TN, Barnes CO, Weisblum Y, Schmidt F, Caskey M, Gaebler C, Cho A, Agudelo M, Finkin S, Wang Z, Poston D, Muecksch F, Hatziioannou T, Bieniasz PD, Robbiani DF, Nussenzweig MC, Bjorkman PJ, Bloom JD
JournalNat Commun
Volume12
Issue1
Pagination4196
Date Published2021 07 07
ISSN2041-1723
KeywordsAntibodies, Monoclonal, Antibodies, Neutralizing, Antibodies, Viral, Binding Sites, COVID-19, Epitopes, HLA Antigens, Humans, Immune Evasion, Models, Molecular, Mutation, Neutralization Tests, Protein Domains, SARS-CoV-2, Spike Glycoprotein, Coronavirus
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.

DOI10.1038/s41467-021-24435-8
Alternate JournalNat Commun
PubMed ID34234131
Grant ListS10 OD028685 / OD / NIH HHS / United States
T32 AI083203 / AI / NIAID NIH HHS / United States
P01 AI138398-S1 / AI / NIAID NIH HHS / United States
U01 AI151698 / AI / NIAID NIH HHS / United States
R01 AI141707 / AI / NIAID NIH HHS / United States
U19 AI111825 / AI / NIAID NIH HHS / United States
R01 AI127893 / AI / NIAID NIH HHS / United States

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