Complete Mapping of Mutations to the SARS-CoV-2 Spike Receptor-Binding Domain that Escape Antibody Recognition

Antibodies targeting the SARS-CoV-2 spike receptor-binding domain (RBD) are being developed as therapeutics and are a major contributor to neutralizing antibody responses elicited by infection. Here, we describe a deep mutational scanning method to map how all amino-acid mutations in the RBD affect...

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Veröffentlicht in:	Cell host & microbe Jg. 29; H. 1; S. 44
Hauptverfasser:	Greaney, Allison J, Starr, Tyler N, Gilchuk, Pavlo, Zost, Seth J, Binshtein, Elad, Loes, Andrea N, Hilton, Sarah K, Huddleston, John, Eguia, Rachel, Crawford, Katharine H D, Dingens, Adam S, Nargi, Rachel S, Sutton, Rachel E, Suryadevara, Naveenchandra, Rothlauf, Paul W, Liu, Zhuoming, Whelan, Sean P J, Carnahan, Robert H, Crowe, Jr, James E, Bloom, Jesse D
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States 13.01.2021
Schlagworte:	Angiotensin-Converting Enzyme 2 - chemistry Angiotensin-Converting Enzyme 2 - metabolism Antibodies, Monoclonal - immunology Antibodies, Neutralizing - immunology Binding Sites Epitopes - immunology Gene Library High-Throughput Nucleotide Sequencing Humans Protein Domains Saccharomyces cerevisiae - genetics SARS-CoV-2 - genetics SARS-CoV-2 - immunology Spike Glycoprotein, Coronavirus - chemistry Spike Glycoprotein, Coronavirus - genetics Spike Glycoprotein, Coronavirus - immunology Spike Glycoprotein, Coronavirus - metabolism antibody escape SARS-CoV-2 deep mutational scanning antigenic evolution
ISSN:	1934-6069, 1934-6069
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Zusammenfassung:	Antibodies targeting the SARS-CoV-2 spike receptor-binding domain (RBD) are being developed as therapeutics and are a major contributor to neutralizing antibody responses elicited by infection. Here, we describe a deep mutational scanning method to map how all amino-acid mutations in the RBD affect antibody binding and apply this method to 10 human monoclonal antibodies. The escape mutations cluster on several surfaces of the RBD that broadly correspond to structurally defined antibody epitopes. However, even antibodies targeting the same surface often have distinct escape mutations. The complete escape maps predict which mutations are selected during viral growth in the presence of single antibodies. They further enable the design of escape-resistant antibody cocktails-including cocktails of antibodies that compete for binding to the same RBD surface but have different escape mutations. Therefore, complete escape-mutation maps enable rational design of antibody therapeutics and assessment of the antigenic consequences of viral evolution.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1934-6069 1934-6069
DOI:	10.1016/j.chom.2020.11.007