严重急性呼吸综合征冠状病毒2（SARS-CoV-2）受体结合域（RBD）逃避单克隆抗体LY-CoV555及其与LY-CoV016的鸡尾酒疗法的突变全图。
Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016.
作者信息
Starr Tyler N, Greaney Allison J, Dingens Adam S, Bloom Jesse D
机构信息
Basic Sciences and Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109.
Department of Genome Sciences, University of Washington, Seattle, WA 98109.
出版信息
bioRxiv. 2021 Feb 22:2021.02.17.431683. doi: 10.1101/2021.02.17.431683.
Monoclonal antibodies and antibody cocktails are a promising therapeutic and prophylaxis for COVID-19. However, ongoing evolution of SARS-CoV-2 can render monoclonal antibodies ineffective. Here we completely map all 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 escape LY-CoV016). Additionally, 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 should diversify the epitopes targeted by antibodies and antibody cocktails to make them more resilient to antigenic evolution of SARS-CoV-2.
单克隆抗体和抗体组合疗法有望用于治疗和预防新冠病毒。然而，新冠病毒不断进化可能导致单克隆抗体失效。在此，我们全面绘制了所有导致严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突蛋白受体结合域（RBD）发生突变从而逃避一种主要单克隆抗体LY-CoV555及其与LY-CoV016的组合抗体结合的情况。在流行的B.1.351和P.1 SARS-CoV-2谱系中，逃避每种抗体结合的单个突变会组合出现（E484K逃避LY-CoV555，K417N/T逃避LY-CoV016）。此外，B.1.429谱系中的L452R突变也逃避LY-CoV555。此外，我们还鉴定出逃避LY-CoV555+LY-CoV016组合抗体的单个氨基酸变化。我们建议，未来的研究应使抗体和抗体组合疗法所靶向的表位多样化，以使其对SARS-CoV-2的抗原进化更具抗性。
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