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快速分离和分析针对 SARS-CoV-2 刺突蛋白的多样化人源单克隆抗体。

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

机构信息

Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, USA.

Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA.

出版信息

Nat Med. 2020 Sep;26(9):1422-1427. doi: 10.1038/s41591-020-0998-x. Epub 2020 Jul 10.

Abstract

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 on the basis of 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.

摘要

抗体是大多数 RNA 病毒免疫的主要决定因素,有希望在重大疫情期间减少感染或疾病。新型冠状病毒 SARS-CoV-2 已导致全球大流行,迄今为止已感染数百万人,造成数十万人死亡。有鉴于此,我们使用了一种快速抗体发现平台来分离数百种针对 SARS-CoV-2 刺突(S)蛋白的人源单克隆抗体(mAbs)。我们根据这些 mAbs 对 S 蛋白亚结构域的反应性以及对 SARS-CoV 的交叉反应性将其分为五个主要类别。其中许多 mAbs 可抑制真正的 SARS-CoV-2 病毒感染,大多数中和 mAbs 识别 S 的受体结合域(RBD)。这项工作定义了 SARS-CoV-2 S 上的脆弱位点,并展示了先进抗体发现平台的速度和稳健性。

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