Cell Rep Med . Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016

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Cell Rep Med


. 2021 Apr 5;100255.
doi: 10.1016/j.xcrm.2021.100255. Online ahead of print.
Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016


Tyler N Starr ¹ , Allison J Greaney ^{1 2 3} , Adam S Dingens ¹ , Jesse D Bloom ^{1 2 4}



Affiliations

• PMID: 33842902
• PMCID: PMC8020059
• DOI: 10.1016/j.xcrm.2021.100255

Abstract

Monoclonal antibodies and antibody cocktails are a promising therapeutic and prophylaxis for coronavirus disease 2019 (COVID-19). However, ongoing evolution of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) can render monoclonal antibodies ineffective. Here, we completely map all of the mutations to the SARS-CoV-2 spike receptor-binding domain (RBD) that escape binding by a leading monoclonal antibody, LY-CoV555, and its cocktail combination with LY-CoV016. Individual mutations that escape binding by each antibody are combined in the circulating B.1.351 and P.1 SARS-CoV-2 lineages (E484K escapes LY-CoV555, K417N/T escapes LY-CoV016). In addition, the L452R mutation in the B.1.429 lineage escapes LY-CoV555. Furthermore, we identify single amino acid changes that escape the combined LY-CoV555+LY-CoV016 cocktail. We suggest that future efforts diversify the epitopes targeted by antibodies and antibody cocktails to make them more resilient to the antigenic evolution of SARS-CoV-2.

Keywords: SARS-CoV-2; antibody escape; bamlanivimab; deep mutational scanning.