Longitudinal isolation of potent near-germline SARS-CoV-2-neutralizing antibodies from COVID-19 patients

  1. Christoph Kreer
  2. Matthias Zehner
  3. Timm Weber
  4. Cornelius Rohde
  5. Sandro Halwe
  6. Meryem S. Ercanoglu
  7. Lutz Gieselmann
  8. Michael Korenkov
  9. Henning Gruell
  10. Philipp Schommers
  11. Kanika Vanshylla
  12. Veronica Di Cristanziano
  13. Hanna Janicki
  14. Reinhild Brinker
  15. Artem Ashurov
  16. Verena Krähling
  17. Alexandra Kupke
  18. Hadas Cohen-Dvashi
  19. Manuel Koch
  20. Simone Lederer
  21. Nico Pfeifer
  22. Timo Wolf
  23. Maria J.G.T. Vehreschild
  24. Clemens Wendtner
  25. Ron Diskin
  26. Stephan Becker
  27. Florian Klein
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Abstract

The SARS-CoV-2 pandemic has unprecedented implications for public health, social life, and world economy. Since approved drugs and vaccines are not available, new options for COVID-19 treatment and prevention are highly demanded. To identify SARS-CoV-2 neutralizing antibodies, we analysed the antibody response of 12 COVID-19 patients from 8 to 69 days post diagnosis. By screening 4,313 SARS-CoV-2-reactive B cells, we isolated 255 antibodies from different time points as early as 8 days post diagnosis. Among these, 28 potently neutralized authentic SARS-CoV-2 (IC100as low as 0.04 μg/ml), showing a broad spectrum of V genes and low levels of somatic mutations. Interestingly, potential precursors were identified in naïve B cell repertoires from 48 healthy individuals that 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 the hope of rapid induction of a protective immune response upon vaccination.

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