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

从新冠肺炎患者体内纵向分离出强效的近种系SARS-CoV-2中和抗体

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作者:Christoph Kreer,Matthias Zehner,Timm Weber,Meryem S Ercanoglu,Lutz Gieselmann,Cornelius Rohde,Sandro Halwe,Michael Korenkov,Philipp Schommers,Kanika Vanshylla,Veronica Di Cristanziano,Hanna Janicki,Reinhild Brinker,Artem Ashurov,Verena Krähling,Alexandra Kupke,Hadas Cohen-Dvashi,Manuel Koch,Jan Mathis Eckert,Simone Lederer,Nico Pfeifer,Timo Wolf,Maria J G T Vehreschild,Clemens Wendtner,Ron Diskin,Henning Gruell,Stephan Becker,Florian Klein

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 IC100 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.

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