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Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies
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Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies
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Journal Article
Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies
2021
Overview
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.
Emerging SARS-CoV-2 mutants may escape neutralization by antibodies. Here, the authors use deep mutational scanning to identify mutations in the RBD that escape human monoclonal antibodies or convalescent plasmas.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/31
/ 38/47
/ 38/70
/ Antibodies, Monoclonal - immunology
/ Antibodies, Neutralizing - immunology
/ Antibodies, Viral - immunology
/ Binding
/ COVID-19
/ Epitopes
/ Humanities and Social Sciences
/ Humans
/ Mutation
/ Science
/ Severe acute respiratory syndrome coronavirus 2
/ Spike Glycoprotein, Coronavirus - chemistry
/ Spike Glycoprotein, Coronavirus - genetics
/ Spike Glycoprotein, Coronavirus - immunology
/ Yeast
