SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape.
SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape.
复制标题
SARS-CoV-2 RBD抗体，最大限度地扩大广度和抵抗逃逸。
DOI：
10.1038/s41586-021-03807-6
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发表时间：
2021-09
期刊：
影响因子：
64.8
通讯作者：
中科院分区：
文献类型：
--
作者：
理想的抗SARS-CoV-2抗体将抵抗病毒逃逸，具有针对多种SARS相关冠状病毒（Sarbecoviruses）的活性，并且通过病毒中和和效应子功能具有高度保护性。了解这些特性如何相互关联以及在表位之间的变化将有助于开发抗体疗法并指导疫苗设计。在这里，我们全面表征逃逸，宽度，并在整个面板的SARS-CoV-2抗体靶向受体结合域（RBD）的效力。尽管在体外中和效力和宽度的Sarbecovirus结合之间的权衡，我们确定具有特殊的Sarbecovirus宽度和相应的抗SARS-CoV-2逃逸的中和抗体。这些抗体之一，S2 H97，在所有的肉瘤病毒进化枝中以高亲和力结合到先前未描述的隐蔽表位，并免疫保护仓鼠免受病毒攻击。靶向ACE 2受体结合基序（RBM）的抗体通常具有差的宽度，并且尽管具有高中和效力，但容易通过突变逃逸。然而，我们表征了一种有效的RBM抗体（S2 E12），其具有与SARS-CoV-2相关的跨Sarbecoviruses的宽度和对病毒逃逸的高屏障。这些数据突出了靶向RBD的抗体之间逃逸、宽度和效力的潜在变化的原则，并确定了针对当前和潜在的未来大流行病的治疗开发的优先级的表位和特征。
An ideal anti-SARS-CoV-2 antibody would resist viral escape, have activity against diverse SARS-related coronaviruses (sarbecoviruses), and be highly protective through viral neutralization and effector functions. Understanding how these properties relate to each other and vary across epitopes would aid development of antibody therapeutics and guide vaccine design. Here, we comprehensively characterize escape, breadth, and potency across a panel of SARS-CoV-2 antibodies targeting the receptor-binding domain (RBD). Despite a tradeoff between in vitro neutralization potency and breadth of sarbecovirus binding, we identify neutralizing antibodies with exceptional sarbecovirus breadth and a corresponding resistance to SARS-CoV-2 escape. One of these antibodies, S2H97, binds with high affinity across all sarbecovirus clades to a previously undescribed cryptic epitope and prophylactically protects hamsters from viral challenge. Antibodies targeting the ACE2 receptor binding motif (RBM) typically have poor breadth and are readily escaped by mutations despite high neutralization potency. Nevertheless, we characterize one potent RBM antibody (S2E12) with breadth across sarbecoviruses related to SARS-CoV-2 and a high barrier to viral escape. These data highlight principles underlying variation in escape, breadth, and potency among antibodies targeting the RBD, and identify epitopes and features to prioritize for therapeutic development against the current and potential future pandemics.
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影响因子：
64.8
作者：
Barnes CO;Jette CA;Abernathy ME;Dam KA;Esswein SR;Gristick HB;Malyutin AG;Sharaf NG;Huey-Tubman KE;Lee YE;Robbiani DF;Nussenzweig MC;West AP Jr;Bjorkman PJ
通讯作者：
Bjorkman PJ
影响因子：
56.9
作者：
Hsieh, Ching-Lin;Goldsmith, Jory A.;McLellan, Jason S.
通讯作者：
McLellan, Jason S.
影响因子：
64.5
作者：
Corti D;Purcell LA;Snell G;Veesler D
通讯作者：
Veesler D
影响因子：
6.7
作者：
Eguia RT;Crawford KHD;Stevens-Ayers T;Kelnhofer-Millevolte L;Greninger AL;Englund JA;Boeckh MJ;Bloom JD
通讯作者：
Bloom JD
影响因子：
4.4
作者：
JORGENSEN, WL;CHANDRASEKHAR, J;KLEIN, ML
通讯作者：
KLEIN, ML