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

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

The SARS-CoV-2 pandemic has unprecedented implications for public health, social life, and the world economy. Because approved drugs and vaccines are 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 (IC(100) as low as 0.04 μg/mL), showing a broad spectrum of variable (V) genes and low levels of somatic mutations. Interestingly, potential precursors 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.