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

Elizaldi, Sonny R.; Lakshmanappa, Yashavanth Shaan; Roh, Jamin W.; Schmidt, Brian A.; Carroll, Timothy D.; Weaver, Kourtney D.; Smith, Justin C.; Deere, Jesse D.; Dutra, Joseph; Stone, Mars; Sammak, Rebecca Lee; Olstad, Katherine J.; Reader, J. Rachel; Ma, Zhong-Min; Nguyen, Nancy K.; Watanabe, Jennifer; Usachaenko, Jodie; Immareddy, Ramya; Yee, JoAnn L.; Weiskopf, Daniela; Sette, Alessandro; Hartigan-O’Connor, Dennis; McSorley, Stephen J.; Morrison, John H.; Tran, Nam K.; Simmons, Graham; Busch, Michael P; Kozlowski, Pamela A.; Van Rompay, Koen K.A.; Miller, Christopher J.; Iyer, Smita S.

CD4 T follicular helper (T(fh)) 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 T(fh) cells 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 T(fh) cells in their peripheral blood on a transitory basis. The CD4 helper cell responses were skewed predominantly toward a T(h)1 response in blood, lung, and lymph nodes, reflective of the interferon-rich cytokine environment following infection. We also observed the generation of germinal center T(fh) cells 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 T(h)1-type T(fh) responses that target the S protein may lead to protective immunity.