SARS-CoV-2 induces robust germinal center CD4 T follicular helper cell responses in rhesus macaques
Yashavanth Shaan Lakshmanappa, Sonny R. Elizaldi, Jamin W. Roh, Brian Schmidt, Timothy D. Carroll, Kourtney D. Weaver, Justin C. Smith, Anil Verma, Jesse D. Deere, Joseph Dutra, Mars Stone, Sergej Franz, Rebecca L. Sammak, Katherine J. Olstad, J. Rachel Reader, Zhong-Min Ma, Nancy K. Nguyen, Jennifer Watanabe, Jodie Usachenko, Ramya Immareddy, JoAnn L. Yee, Daniela Weiskopf, Alessandro Sette, Dennis J. Hartigan-O’Connor, Stephen J. McSorley, John H. Morrison, Nam K. Tran, Graham Simmons, Michael P. Busch, Pamela A. Kozlowski, Koen K. A. Van Rompay, Christopher J. Miller, Smita S. Iyer
Abstract
Abstract 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.