SARS-CoV-2 infection induces germinal center responses with robust stimulation of CD4 T follicular helper cells in rhesus macaques

Sonny R. Elizaldi; Yashavanth Shaan Lakshmanappa; Jamin W. Roh; Brian A. Schmidt; Timothy D. Carroll; Kourtney D. Weaver; Justin C. Smith; Jesse D. Deere; Joseph Dutra; Mars Stone; Rebecca Lee Sammak; Katherine J. Olstad; J. Rachel Reader; Zhong-Min Ma; Nancy K. Nguyen; Jennifer Watanabe; Jodie Usachaenko; Ramya Immareddy; JoAnn 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

doi:10.1101/2020.07.07.191007

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bioRxiv · 10.1101/2020.07.07.191007

SARS-CoV-2 infection induces germinal center responses with robust stimulation of CD4 T follicular helper cells in rhesus macaques

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Abstract

CD4 T follicular helper (Tfh) cells are important for the generation of long-lasting and specific humoral protection against viral infections. The degree to which SARS-CoV-2 infection generates Tfh cells and stimulates the germinal center response is an important question as we investigate vaccine options for the current pandemic. Here we report that, following infection with SARS-CoV-2, adult rhesus macaques exhibited transient accumulation of activated, proliferating Tfh cells in their peripheral blood on a transitory basis. The CD4 helper cell responses were skewed predominantly toward a Th1 response in blood, lung, and lymph nodes, reflective of the interferon-rich cytokine environment following infection. We also observed the generation of germinal center Tfh cells specific for the SARS-CoV-2 spike (S) and nucleocapsid (N) proteins, and a corresponding early appearance of antiviral serum IgG antibodies but delayed or absent IgA antibodies. Our data suggest that a vaccine promoting Th1-type Tfh responses that target the S protein may lead to protective immunity.

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Sonny R. Elizaldi, Yashavanth Shaan Lakshmanappa, Jamin W. Roh, Brian A. Schmidt, Timothy D. Carroll, Kourtney D. Weaver, Justin C. Smith, Jesse D. Deere, Joseph Dutra, Mars Stone, Rebecca Lee Sammak, Katherine J. Olstad, J. Rachel Reader, Zhong-Min Ma, Nancy K. Nguyen, Jennifer Watanabe, Jodie Usachaenko, Ramya Immareddy, JoAnn 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. 2020-07-08. SARS-CoV-2 infection induces germinal center responses with robust stimulation of CD4 T follicular helper cells in rhesus macaques. https://doi.org/10.1101/2020.07.07.191007

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