Longitudinal Isolation of Potent Near-Germline SARS-CoV-2-Neutralizing Antibodies from COVID-19 Patients
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, 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.
Keywords: 2019-nCoV; COVID-19; SARS-CoV-2; monoclonal antibody; neutralizing antibody; single B cell analysis.
Conflict of interest statement
Declaration of Interests A patent application encompassing aspects of this work has been filed by the University of Cologne, listing F.K., S.B., C.K., M.Z., and H.G. as inventors.
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
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