Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition

By Allison J. Greaney, Tyler N. Starr, P. Gilchuk, Seth J. Zost, E. Binshtein, Andrea N. Loes, Sarah K. Hilton, J. Huddleston, Rachel T. Eguia, K. H. Crawford and 10 more. bioRxiv, 2020

934 citations recorded by the source corpus.

Antibodies targeting the SARS-CoV-2 spike receptor-binding domain (RBD) are being developed as therapeutics and make a major contribution to the neutralizing antibody response 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 RBD surface often have distinct escape mutations. The complete escape maps predict which mutations are selected during viral growth in the presence of single antibodies, and enable us to design escape-resistant antibody cocktails–including cocktails of antibodies that compete for binding to the same surface of the RBD 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.

Subfields: Infectious Diseases, Molecular Biology, Radiology, Nuclear Medicine and Imaging

View Paper: https://www.semanticscholar.org/paper/68e472088c3a06970be75e121ff8e987b99add76

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In Infectious Diseases

Jesse D. Bloom

In Molecular Biology

In Radiology, Nuclear Medicine and Imaging

Citations in the corpus

Rapid generation of potent antibodies by autonomous hypermutation in yeast (2020, positive): “In fact, we estimate that given an SARS-CoV-2 RBD escape variant (28) we would be able to discover multiple high-affinity binders in 2 weeks.”
A human coronavirus evolves antigenically to escape antibody immunity (2020, background): “…it is ominous that mutations affecting neutralization by antibodies or sera are already present at low frequencies among circulating SARS-CoV-2 (Greaney et al., 2020; Kemp, 2020; Liu et al., 2020b; McCarthy et al., 2020; Starr et al., 2020b; Thomson, 2020; Weisblum et al., 2020) even though…”