Longitudinal Isolation of Potent Near-Germline SARS-CoV-2-Neutralizing Antibodies from COVID-19 Patients
Longitudinal Isolation of Potent Near-Germline SARS-CoV-2-Neutralizing Antibodies from COVID-19 Patients
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DOI：
10.1016/j.cell.2020.06.044
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发表时间：
2020-08-20
期刊：
影响因子：
64.5
通讯作者：
Klein, Florian
中科院分区：
文献类型：
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作者：
Kreer, Christoph;Zehner, Matthias;Klein, Florian
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。由于获得批准的药物和疫苗有限或无法获得，因此对新冠肺炎治疗和预防的新选择需求很高。为了鉴定SARS-CoV-2中和抗体，我们分析了12例新冠肺炎患者在确诊后第8~69天的抗体反应。通过对4,313个SARS-CoV-2反应性B细胞的筛选，我们从不同时间点分离出255个抗体，最早在确诊后8天。其中，28个有效地中和了正宗的SARS-CoV-2，IC100低至0.04微克/毫升，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48名健康个体的幼稚B细胞库中发现了潜在的前体序列，这些人在新冠肺炎大流行之前进行了采样。我们的结果表明，SARS-CoV-2中和抗体很容易从不同的前体细胞池中产生，这为疫苗接种后快速诱导保护性免疫反应带来了希望。
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 IC100 as low as 0.04 mu g/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.