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从 COVID-19 患者中分离出具有强大接近种系 SARS-CoV-2 中和抗体的纵向研究。

Longitudinal Isolation of Potent Near-Germline SARS-CoV-2-Neutralizing Antibodies from COVID-19 Patients.

机构信息

Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.

Institute of Virology, Faculty of Medicine, Philipps University Marburg, 35043 Marburg, Germany; German Center for Infection Research, Partner Site Gießen-Marburg-Langen, 35043 Marburg, Germany.

出版信息

Cell. 2020 Aug 20;182(4):843-854.e12. doi: 10.1016/j.cell.2020.06.044. Epub 2020 Jul 13.

Abstract

The SARS-CoV-2 pandemic has unprecedented implications for public health, social life, and the world economy. Because approved drugs and vaccines are limited or not available, new options for COVID-19 treatment and prevention are in high demand. To identify SARS-CoV-2-neutralizing antibodies, we analyzed the antibody response of 12 COVID-19 patients from 8 to 69 days after diagnosis. By screening 4,313 SARS-CoV-2-reactive B cells, we isolated 255 antibodies from different time points as early as 8 days after diagnosis. Of these, 28 potently neutralized authentic SARS-CoV-2 with IC as low as 0.04 μg/mL, showing a broad spectrum of variable (V) genes and low levels of somatic mutations. Interestingly, potential precursor sequences were identified in naive B cell repertoires from 48 healthy individuals who were sampled before the COVID-19 pandemic. Our results demonstrate that SARS-CoV-2-neutralizing antibodies are readily generated from a diverse pool of precursors, fostering hope for rapid induction of a protective immune response upon vaccination.

摘要

SARS-CoV-2 大流行对公共卫生、社会生活和世界经济产生了前所未有的影响。由于批准的药物和疫苗有限或不可用,因此对 COVID-19 治疗和预防的新选择的需求很高。为了鉴定 SARS-CoV-2 中和抗体,我们分析了 12 名 COVID-19 患者在诊断后 8 至 69 天的抗体反应。通过筛选 4313 个对 SARS-CoV-2 有反应的 B 细胞,我们从最早在诊断后 8 天的不同时间点分离出了 255 种抗体。其中,28 种抗体能够强有力地中和真实的 SARS-CoV-2,IC50 低至 0.04μg/mL,显示出广泛的可变(V)基因和低水平的体细胞突变。有趣的是,在 COVID-19 大流行之前采样的 48 名健康个体的未成熟 B 细胞库中鉴定出了潜在的前体序列。我们的结果表明,SARS-CoV-2 中和抗体很容易从多样化的前体池中产生,为接种疫苗后迅速诱导保护性免疫反应带来了希望。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fad/7445432/691a206b5c83/fx1.jpg

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