Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein.

Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein.
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DOI:
10.1038/s41591-020-0998-x
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发表时间:
2020-09
期刊:
影响因子:
82.9
通讯作者:
Crowe JE Jr
Crowe JE Jr
中科院分区:
医学1区
文献类型:
--
作者:
Zost SJ;Gilchuk P;Chen RE;Case JB;Reidy JX;Trivette A;Nargi RS;Sutton RE;Suryadevara N;Chen EC;Binshtein E;Shrihari S;Ostrowski M;Chu HY;Didier JE;MacRenaris KW;Jones T;Day S;Myers L;Eun-Hyung Lee F;Nguyen DC;Sanz I;Martinez DR;Rothlauf PW;Bloyet LM;Whelan SPJ;Baric RS;Thackray LB;Diamond MS;Carnahan RH;Crowe JE Jr

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抗体是大多数 RNA 病毒免疫的主要决定因素,有望在重大流行病期间减少感染或疾病。新型冠状病毒 SARS-CoV-2 已引起全球大流行,迄今为止已造成数百万人感染和数十万人死亡。为此,我们使用快速抗体发现平台分离了数百种针对 SARS-CoV-2 刺突 (S) 蛋白的人单克隆抗体 (mAb)。我们根据这些单克隆抗体对 S 蛋白子结构域的反应性以及与 SARS-CoV 的交叉反应性,将其分为五个主要类别。其中许多单克隆抗体可抑制真正的 SARS-CoV-2 病毒的感染,其中大多数中和单克隆抗体可识别 S 的受体结合域 (RBD)。这项工作定义了 SARS-CoV-2 S 的脆弱位点,并展示了先进抗体发现平台的速度和稳健性。
Antibodies are a principal determinant of immunity for most RNA viruses and have promise to reduce infection or disease during major epidemics. The novel coronavirus SARS-CoV-2 has caused a global pandemic with millions of infections and hundreds of thousands of deaths to date. In response, we used a rapid antibody discovery platform to isolate hundreds of human monoclonal antibodies (mAbs) against the SARS-CoV-2 spike (S) protein. We stratify these mAbs into five major classes based on their reactivity to subdomains of S protein as well as their cross-reactivity to SARS-CoV. Many of these mAbs inhibit infection of authentic SARS-CoV-2 virus, with most neutralizing mAbs recognizing the receptor-binding domain (RBD) of S. This work defines sites of vulnerability on SARS-CoV-2 S and demonstrates the speed and robustness of advanced antibody discovery platforms.
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