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 A. Schmidt, Timothy D. Carroll, Kourtney D. Weaver, Justin C. Smith, Anil Verma, Jesse D. Deere, Joseph Dutra, Mars Stone, Sergej Franz, Rebecca Lee Sammak, Katherine J. Olstad, J. Rachel Reader, Zhong Min Ma, Nancy K. Nguyen, Jennifer Watanabe, Jodie Usachenko, Ramya ImmareddyJo Ann L. Yee, Daniela Weiskopf, Alessandro Sette, Dennis 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

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49 Scopus citations


CD4 T follicular helper (Tfh) cells are important for the generation of durable and specific humoral protection against viral infections. The degree to which SARS-CoV-2 infection generates Tfh 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 Tfh cells with a Th1 profile in peripheral blood. CD4 helper cell responses skewed predominantly toward a Th1 response in blood, lung, and lymph nodes. SARS-CoV-2 Infection induced GC Tfh 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.

Original languageEnglish
Article number541
JournalNature Communications
Issue number1
StatePublished - Dec 2021
Externally publishedYes


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