SARS-CoV-2 infection induces robust germinal center CD4 T follicular helper cell responses in rhesus macaques

CD4 T follicular helper (T(fh)) cells are important for the generation of durable 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 SARS-CoV-2 infection resulted in transient accumulation of pro-inflammatory monocytes and proliferating T(fh) cells with a T(h)1 profile in peripheral blood. CD4 helper cell responses were skewed predominantly toward a T(h)1 response in blood, lung, and lymph nodes. We 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. Our data suggest that a vaccine promoting T(h)1-type T(fh) responses that target the S protein may lead to protective immunity.