Summary 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. Graphical abstract Highlights Map of all SARS-CoV-2 mutations that escape LY-CoV555 (bamlanivimab) antibody binding LY-CoV555 is sensitive to mutations E484K and L452R in variants of concern Single mutations and circulating combinations escape the LY-CoV555/LY-CoV016 cocktail Therapeutic antibodies that target subdominant epitopes are needed Starr et al. report a complete map of all of the SARS-CoV-2 mutations that escape binding by the LY-CoV555 (bamlanivimab) antibody and its cocktail with LY-CoV016. These maps highlight high-frequency mutations that may affect LY-CoV555 efficacy and enable immediate interpretation of the effects of future viral variation on this antibody.
【저자키워드】 SARS-CoV-2, bamlanivimab, antibody escape, deep mutational scanning, 【초록키워드】 COVID-19, coronavirus disease, Evolution, Efficacy, Mutation, antibody, B.1.351, monoclonal antibody, Variation, variants of concern, Prophylaxis, Antibody binding, antibody cocktail, L452R, RBD, P.1, therapeutic, Interpretation, Lineage, B.1.429, E484K, spike receptor-binding domain, Therapeutic antibody, SARS-CoV-2 mutation, epitope, LY-CoV555, binding, Combination, Abstract, individual, effort, antigenic evolution, circulating, SARS-CoV-2 lineage, Effect, Affect, Complete, highlight, amino acid change, identify, addition, Map, the SARS-CoV-2, 【제목키워드】 Mutation, monoclonal antibody, LY-CoV555, SARS-CoV-2 RBD,