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

ABSTRACT: 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

SUBMITTER: Greaney AJ 

PROVIDER: S-EPMC7491521 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature