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

Shaan Lakshmanappa, Yashavanth; Elizaldi, Sonny R.; Roh, Jamin W.; Schmidt, Brian A.; Carroll, Timothy D.; Weaver, Kourtney D.; Smith, Justin C.; Verma, Anil; Deere, Jesse D.; Dutra, Joseph; Stone, Mars; Franz, Sergej; Sammak, Rebecca Lee; Olstad, Katherine J.; Rachel Reader, J.; Ma, Zhong-Min; Nguyen, Nancy K.; Watanabe, Jennifer; Usachenko, 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 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 (GC) response is an important question as we investigate vaccine induced immunity against COVID-19. Here, we report that SARS-CoV-2 infection in rhesus macaques, either infused with convalescent plasma, normal plasma, or receiving no infusion, 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 skewed predominantly toward a T(h)1 response in blood, lung, and lymph nodes. SARS-CoV-2 Infection induced GC T(fh) cells specific for the SARS-CoV-2 spike and nucleocapsid proteins, and a corresponding early appearance of antiviral serum IgG antibodies. Collectively, the data show induction of GC responses in a rhesus model of mild COVID-19.