Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016.
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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DOI：
10.1016/j.xcrm.2021.100255
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发表时间：
2021-04-20
期刊：
影响因子：
--
通讯作者：
Bloom JD
中科院分区：
文献类型：
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作者：
Starr TN;Greaney AJ;Dingens AS;Bloom JD
单克隆抗体和抗体混合物是2019冠状病毒病（COVID-19）的一种有前途的治疗和预防方法。然而，严重急性呼吸道综合征-冠状病毒-2（SARS-CoV-2）的不断演变可使单克隆抗体无效。在这里，我们完全映射到SARS-CoV-2刺突受体结合结构域（RBD）的突变逃脱了领先的单克隆抗体，LY-CoV 555，及其与LY-CoV 016的鸡尾酒组合的结合。逃避每种抗体结合的个体突变在循环B.1.351和P.1 SARS-CoV-2谱系中组合（E484 K逃避LY-CoV 555，K417 N/T逃避LY-CoV 016）。此外，B.1.429谱系中的L452 R突变逃脱了LY-CoV 555。此外，我们鉴定了逃避组合的LY-CoV 555 + LY-CoV 016混合物的单个氨基酸变化。我们建议，未来的努力多样化的抗体和抗体鸡尾酒靶向的表位，使他们更有弹性的SARS-CoV-2的抗原进化。图所有SARS-CoV-2突变逃脱LY-CoV 555（bamlanivimab）抗体结合LY-CoV 555是敏感的突变E484 K和L452 R在变异的关注单一突变和循环组合逃脱LY-CoV 555/LY-CoV 016鸡尾酒需要靶向亚显性表位的治疗抗体Starr et al.报告了逃避LY-CoV 555（bamlanivimab）抗体及其与LY-CoV 016混合物结合的所有SARS-CoV-2突变的完整图谱。这些图谱突出了可能影响LY-CoV 555疗效的高频突变，并能够立即解释未来病毒变异对该抗体的影响。
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. 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.