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

Elizaldi, Sonny; Lakshmanappa, Yashavanth Shaan; Roh, Jamin; Schmidt, Brian; Carroll, Timothy; Weaver, Kourtney; Smith, Justin; Deere, Jesse; Dutra, Joseph; Stone, Mars; Franz, Sergej; Sammak, Rebecca; Olstad, Katherine; Reader, J. Rachel; Ma, Zhong-Min; Nguyen, Nancy; Watanabe, Jennifer; Usachenko, Jodie; Immareddy, Ramya; Yee, JoAnn; Weiskopf, Daniela; Sette, Alessandro; Hartigan-O'Connor, Dennis; McSorley, Stephen; Morrison, John; Tran, Nam; Simmons, Graham; Busch, Michael; Kozlowsk, Pamela; van Rompay, Koen; Miller, Christopher; Iyer, Smita

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.