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来自 COVID-19 患者的强效中和抗体定义了多个易损目标。

Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability.

机构信息

Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.

Department of Internal Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.

出版信息

Science. 2020 Aug 7;369(6504):643-650. doi: 10.1126/science.abc5902. Epub 2020 Jun 15.

DOI:10.1126/science.abc5902
PMID:32540902
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7299281/
Abstract

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a large impact on global health, travel, and economy. Therefore, preventative and therapeutic measures are urgently needed. Here, we isolated monoclonal antibodies from three convalescent coronavirus disease 2019 (COVID-19) patients using a SARS-CoV-2 stabilized prefusion spike protein. These antibodies had low levels of somatic hypermutation and showed a strong enrichment in VH1-69, VH3-30-3, and VH1-24 gene usage. A subset of the antibodies was able to potently inhibit authentic SARS-CoV-2 infection at a concentration as low as 0.007 micrograms per milliliter. Competition and electron microscopy studies illustrate that the SARS-CoV-2 spike protein contains multiple distinct antigenic sites, including several receptor-binding domain (RBD) epitopes as well as non-RBD epitopes. In addition to providing guidance for vaccine design, the antibodies described here are promising candidates for COVID-19 treatment and prevention.

摘要

严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)的迅速传播对全球健康、旅行和经济产生了重大影响。因此,迫切需要预防和治疗措施。在这里,我们使用稳定的 SARS-CoV-2 预融合刺突蛋白从三名康复的 2019 年冠状病毒病(COVID-19)患者中分离出单克隆抗体。这些抗体体细胞超突变水平低,并显示出 VH1-69、VH3-30-3 和 VH1-24 基因使用的强烈富集。一组抗体能够以低至每毫升 0.007 微克的浓度强烈抑制真正的 SARS-CoV-2 感染。竞争和电子显微镜研究表明,SARS-CoV-2 刺突蛋白包含多个不同的抗原位点,包括多个受体结合域(RBD)表位和非 RBD 表位。除了为疫苗设计提供指导外,这里描述的抗体也是 COVID-19 治疗和预防的有希望的候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d39/7299281/424ed275c4b2/369_643_F5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d39/7299281/77f5d271bd7f/369_643_F1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d39/7299281/1f4e80649222/369_643_F2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d39/7299281/8515ff22384e/369_643_F3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d39/7299281/eede29ac9022/369_643_F4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d39/7299281/424ed275c4b2/369_643_F5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d39/7299281/77f5d271bd7f/369_643_F1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d39/7299281/1f4e80649222/369_643_F2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d39/7299281/8515ff22384e/369_643_F3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d39/7299281/eede29ac9022/369_643_F4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d39/7299281/424ed275c4b2/369_643_F5.jpg

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