Broad sarbecovirus neutralizing antibodies define a key site of vulnerability on the SARS-CoV-2 spike protein

  1. Anna Z. Wec
  2. Daniel Wrapp
  3. Andrew S. Herbert
  4. Daniel Maurer
  5. Denise Haslwanter
  6. Mrunal Sakharkar
  7. Rohit K. Jangra
  8. M. Eugenia Dieterle
  9. Asparouh Lilov
  10. Deli Huang
  11. Longping V. Tse
  12. Nicole V. Johnson
  13. Ching-Lin Hsieh
  14. Nianshuang Wang
  15. Juergen H. Nett
  16. Elizabeth Champney
  17. Irina Burnina
  18. Michael Brown
  19. Shu Lin
  20. Melanie Sinclair
  21. Carl Johnson
  22. Sarat Pudi
  23. Robert Bortz
  24. Ariel S. Wirchnianski
  25. Ethan Laudermilch
  26. Catalina Florez
  27. J. Maximilian Fels
  28. Cecilia M. O’Brien
  29. Barney S. Graham
  30. David Nemazee
  31. Dennis R. Burton
  32. Ralph S. Baric
  33. James E. Voss
  34. Kartik Chandran
  35. John M. Dye
  36. Jason S. McLellan
  37. Laura M. Walker
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Abstract

Broadly protective vaccines against known and pre-emergent coronaviruses are urgently needed. Critical to their development is a deeper understanding of cross-neutralizing antibody responses induced by natural human coronavirus (HCoV) infections. Here, we mined the memory B cell repertoire of a convalescent SARS donor and identified 200 SARS-CoV-2 binding antibodies that target multiple conserved sites on the spike (S) protein. A large proportion of the antibodies display high levels of somatic hypermutation and cross-react with circulating HCoVs, suggesting recall of pre-existing memory B cells (MBCs) elicited by prior HCoV infections. Several antibodies potently cross-neutralize SARS-CoV, SARS-CoV-2, and the bat SARS-like virus WIV1 by blocking receptor attachment and inducing S1 shedding. These antibodies represent promising candidates for therapeutic intervention and reveal a new target for the rational design of pan-sarbecovirus vaccines.

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