Immune Correlates of Protection by mRNA-1273 Immunization against SARS-CoV-2 Infection in Nonhuman Primates

  1. Kizzmekia S. Corbett
  2. Martha C. Nason
  3. Britta Flach
  4. Matthew Gagne
  5. Sarah O’ Connell
  6. Timothy S. Johnston
  7. Shruti N. Shah
  8. Venkata Viswanadh Edara
  9. Katharine Floyd
  10. Lilin Lai
  11. Charlene McDanal
  12. Joseph R. Francica
  13. Barbara Flynn
  14. Kai Wu
  15. Angela Choi
  16. Matthew Koch
  17. Olubukola M. Abiona
  18. Anne P. Werner
  19. Gabriela S. Alvarado
  20. Shayne F. Andrew
  21. Mitzi M. Donaldson
  22. Jonathan Fintzi
  23. Dillon R. Flebbe
  24. Evan Lamb
  25. Amy T. Noe
  26. Saule T. Nurmukhambetova
  27. Samantha J. Provost
  28. Anthony Cook
  29. Alan Dodson
  30. Andrew Faudree
  31. Jack Greenhouse
  32. Swagata Kar
  33. Laurent Pessaint
  34. Maciel Porto
  35. Katelyn Steingrebe
  36. Daniel Valentin
  37. Serge Zouantcha
  38. Kevin W. Bock
  39. Mahnaz Minai
  40. Bianca M. Nagata
  41. Juan I. Moliva
  42. Renee van de Wetering
  43. Seyhan Boyoglu-Barnum
  44. Kwanyee Leung
  45. Wei Shi
  46. Eun Sung Yang
  47. Yi Zhang
  48. John-Paul M. Todd
  49. Lingshu Wang
  50. Hanne Andersen
  51. Kathryn E. Foulds
  52. Darin K. Edwards
  53. John R. Mascola
  54. Ian N. Moore
  55. Mark G. Lewis
  56. Andrea Carfi
  57. David Montefiori
  58. Mehul S. Suthar
  59. Adrian McDermott
  60. Nancy J. Sullivan
  61. Mario Roederer
  62. Daniel C. Douek
  63. Barney S. Graham
  64. Robert A. Seder
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Abstract

Immune correlates of protection can be used as surrogate endpoints for vaccine efficacy. The nonhuman primate (NHP) model of SARS-CoV-2 infection replicates key features of human infection and may be used to define immune correlates of protection following vaccination. Here, NHP received either no vaccine or doses ranging from 0.3 – 100 μg of mRNA-1273, a mRNA vaccine encoding the prefusion-stabilized SARS-CoV-2 spike (S-2P) protein encapsulated in a lipid nanoparticle. mRNA-1273 vaccination elicited robust circulating and mucosal antibody responses in a dose-dependent manner. Viral replication was significantly reduced in bronchoalveolar lavages and nasal swabs following SARS-CoV-2 challenge in vaccinated animals and was most strongly correlated with levels of anti-S antibody binding and neutralizing activity. Consistent with antibodies being a correlate of protection, passive transfer of vaccine-induced IgG to naïve hamsters was sufficient to mediate protection. Taken together, these data show that mRNA-1273 vaccine-induced humoral immune responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP.

One-Sentence Summary

mRNA-1273 vaccine-induced antibody responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP.

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