SARS-CoV-2 vaccination induces neutralizing antibodies against pandemic and pre-emergent SARS-related coronaviruses in monkeys

  1. Kevin O. Saunders
  2. Esther Lee
  3. Robert Parks
  4. David R. Martinez
  5. Dapeng Li
  6. Haiyan Chen
  7. Robert J. Edwards
  8. Sophie Gobeil
  9. Maggie Barr
  10. Katayoun Mansouri
  11. S. Munir Alam
  12. Laura L. Sutherland
  13. Fangping Cai
  14. Aja M. Sanzone
  15. Madison Berry
  16. Kartik Manne
  17. Anyway B. Kapingidza
  18. Mihai Azoitei
  19. Longping V. Tse
  20. Trevor D. Scobey
  21. Rachel L. Spreng
  22. R. Wes Rountree
  23. C. Todd DeMarco
  24. Thomas N. Denny
  25. Christopher W. Woods
  26. Elizabeth W. Petzold
  27. Thomas H. Oguin
  28. Gregory D. Sempowski
  29. Matthew Gagne
  30. Daniel C. Douek
  31. Mark A. Tomai
  32. Christopher B. Fox
  33. Robert Seder
  34. Kevin Wiehe
  35. Drew Weissman
  36. Norbert Pardi
  37. Priyamvada Acharya
  38. Hanne Andersen
  39. Mark G. Lewis
  40. Ian N. Moore
  41. David C. Montefiori
  42. Ralph S. Baric
  43. Barton F. Haynes
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Abstract

Betacoronaviruses (betaCoVs) caused the severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) outbreaks, and now the SARS-CoV-2 pandemic. Vaccines that elicit protective immune responses against SARS-CoV-2 and betaCoVs circulating in animals have the potential to prevent future betaCoV pandemics. Here, we show that immunization of macaques with a multimeric SARS-CoV-2 receptor binding domain (RBD) nanoparticle adjuvanted with 3M-052-Alum elicited cross-neutralizing antibody responses against SARS-CoV-1, SARS-CoV-2, batCoVs and the UK B.1.1.7 SARS-CoV-2 mutant virus. Nanoparticle vaccination resulted in a SARS-CoV-2 reciprocal geometric mean neutralization titer of 47,216, and robust protection against SARS-CoV-2 in macaque upper and lower respiratory tracts. Importantly, nucleoside-modified mRNA encoding a stabilized transmembrane spike or monomeric RBD protein also induced SARS-CoV-1 and batCoV cross-neutralizing antibodies, albeit at lower titers. These results demonstrate current mRNA vaccines may provide some protection from future zoonotic betaCoV outbreaks, and provide a platform for further development of pan-betaCoV nanoparticle vaccines.

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