SARS-CoV-2 infection induces germinal center responses with robust stimulation of CD4 T follicular helper cells in rhesus macaques

  1. Sonny R. Elizaldi
  2. Yashavanth Shaan Lakshmanappa
  3. Jamin W. Roh
  4. Brian A. Schmidt
  5. Timothy D. Carroll
  6. Kourtney D. Weaver
  7. Justin C. Smith
  8. Jesse D. Deere
  9. Joseph Dutra
  10. Mars Stone
  11. Rebecca Lee Sammak
  12. Katherine J. Olstad
  13. J. Rachel Reader
  14. Zhong-Min Ma
  15. Nancy K. Nguyen
  16. Jennifer Watanabe
  17. Jodie Usachaenko
  18. Ramya Immareddy
  19. JoAnn L. Yee
  20. Daniela Weiskopf
  21. Alessandro Sette
  22. Dennis Hartigan-O’Connor
  23. Stephen J. McSorley
  24. John H. Morrison
  25. Nam K. Tran
  26. Graham Simmons
  27. Michael P Busch
  28. Pamela A. Kozlowski
  29. Koen K.A. Van Rompay
  30. Christopher J. Miller
  31. Smita S. Iyer
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Abstract

CD4 T follicular helper (Tfh) cells are important for the generation of long-lasting and specific humoral protection against viral infections. The degree to which SARS-CoV-2 infection generates Tfhcells and stimulates the germinal center response is an important question as we investigate vaccine options for the current pandemic. Here we report that, following infection with SARS-CoV-2, adult rhesus macaques exhibited transient accumulation of activated, proliferating Tfhcells in their peripheral blood on a transitory basis. The CD4 helper cell responses were skewed predominantly toward a Th1 response in blood, lung, and lymph nodes, reflective of the interferon-rich cytokine environment following infection. We also observed the generation of germinal center Tfhcells specific for the SARS-CoV-2 spike (S) and nucleocapsid (N) proteins, and a corresponding early appearance of antiviral serum IgG antibodies but delayed or absent IgA antibodies. Our data suggest that a vaccine promoting Th1-type Tfh responses that target the S protein may lead to protective immunity.

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