Deep mutational scanning to predict antibody escape in SARS-CoV-2 Omicron subvariants

The major concern of COVID-19 therapeutic monoclonal antibodies is the loss of efficacy to continuously emerging SARS-CoV-2 variants. To predict the antibodies efficacy to the future Omicron subvariants, we conducted deep mutational scanning (DMS) encompassing all single mutations in the receptor binding domain of BA.2 strain. In case of bebtelovimab that preserves neutralization activity against BA.2 and BA.5, broad range of amino acid substitutions at K444, V445 and G446 and some substitutions at P499 and T500 were indicated to achieve the antibody escape. Among currently increasing subvariants, BA2.75 carrying G446S partly and XBB with V445P and BQ.1 with K444T completely evade the neutralization of bebtelovimab, consistent with the DMS results. DMS can comprehensively characterize the antibody escape for efficient and effective management of future variants.