Starr Tyler N, Greaney Allison J, Dingens Adam S, Bloom Jesse D
Basic Sciences and Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Department of Genome Sciences, University of Washington, Seattle, WA 98109, USA.
Cell Rep Med. 2021 Apr 20;2(4):100255. doi: 10.1016/j.xcrm.2021.100255. Epub 2021 Apr 5.
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.
单克隆抗体和抗体鸡尾酒疗法是治疗和预防2019冠状病毒病（COVID-19）的一种有前景的方法。然而，严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的不断进化可能会使单克隆抗体失效。在此，我们全面绘制了所有导致一种领先的单克隆抗体LY-CoV555及其与LY-CoV016的鸡尾酒组合无法结合的SARS-CoV-2刺突受体结合域（RBD）突变。在循环的B.1.351和P.1 SARS-CoV-2谱系中，每个抗体无法结合的单个突变组合在一起（E484K突变使LY-CoV555无法结合，K417N/T突变使LY-CoV016无法结合）。此外，B.1.429谱系中的L452R突变使LY-CoV555无法结合。此外，我们还确定了能逃避LY-CoV555+LY-CoV016鸡尾酒组合的单个氨基酸变化。我们建议未来的研究应使抗体和抗体鸡尾酒所靶向的表位多样化，以使它们对SARS-CoV-2的抗原进化更具抗性。
