Prospective mapping of viral mutations that escape antibodies used to treat COVID-19.
Prospective mapping of viral mutations that escape antibodies used to treat COVID-19.
复制标题
DOI：
10.1126/science.abf9302
复制
发表时间：
2021-02-19
期刊：
影响因子：
--
通讯作者：
Bloom JD
中科院分区：
文献类型：
--
作者：
Starr TN;Greaney AJ;Addetia A;Hannon WW;Choudhary MC;Dingens AS;Li JZ;Bloom JD
几种抗体正在使用或正在开发中作为治疗COVID-19的疗法。随着新的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变异体的出现，预测它们是否会对抗体治疗保持敏感是很重要的。Starr等人使用了一个酵母文库，该文库涵盖了SARS-CoV-2受体结合结构域的所有突变，这些突变不会强烈破坏与宿主受体（ACE 2）的结合，并绘制了这些突变如何影响与三种主要抗SARS-CoV-2抗体的结合。图谱鉴定了逃避抗体结合的突变，包括逃避Regeneron抗体混合物中两种抗体的单个突变。许多逃避单一抗体的突变在人群中循环。SARS-CoV-2突变的完整图谱可以逃脱Regeneron单克隆抗体鸡尾酒，这有助于解释治疗患者的病毒进化。抗体是严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的潜在疗法，但病毒进化以逃避它们的风险仍不清楚。在这里，我们绘制了SARS-CoV-2受体结合结构域（RBD）的所有突变如何影响REGN-COV 2混合物中抗体和抗体LY-CoV 016的结合。这些完整图谱揭示了一个完全逃脱REGN-COV 2混合物的单个氨基酸突变，该混合物由两种抗体REGN 10933和REGN 10987组成，靶向不同的结构表位。图谱还鉴定了在接受REGN-COV 2治疗的持续感染患者中以及在体外病毒逃逸选择期间选择的病毒突变。最后，图谱显示，逃避单个抗体的突变已经存在于流行的SARS-CoV-2菌株中。这些完整的逃逸图谱能够解释病毒监测期间观察到的突变后果。
Several antibodies are in use or under development as therapies to treat COVID-19. As new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants emerge, it is important to predict whether they will remain susceptible to antibody treatment. Starr et al. used a yeast library that covers all mutations to the SARS-CoV-2 receptor-binding domain that do not strongly disrupt binding to the host receptor (ACE2) and mapped how these mutations affect binding to three leading anti–SARS-CoV-2 antibodies. The maps identify mutations that escape antibody binding, including a single mutation that escapes both antibodies in the Regeneron antibody cocktail. Many of the mutations that escape single antibodies are circulating in the human population. Science, this issue p. 850 Complete maps of SARS-CoV-2 mutations that escape the Regeneron monoclonal antibody cocktail help explain viral evolution in a treated patient. Antibodies are a potential therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the risk of the virus evolving to escape them remains unclear. Here we map how all mutations to the receptor binding domain (RBD) of SARS-CoV-2 affect binding by the antibodies in the REGN-COV2 cocktail and the antibody LY-CoV016. These complete maps uncover a single amino acid mutation that fully escapes the REGN-COV2 cocktail, which consists of two antibodies, REGN10933 and REGN10987, targeting distinct structural epitopes. The maps also identify viral mutations that are selected in a persistently infected patient treated with REGN-COV2 and during in vitro viral escape selections. Finally, the maps reveal that mutations escaping the individual antibodies are already present in circulating SARS-CoV-2 strains. These complete escape maps enable interpretation of the consequences of mutations observed during viral surveillance.