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 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. Rompay (), Christopher J. Miller () and Smita S. Iyer ()
Additional contact information
Yashavanth Shaan Lakshmanappa: UC Davis
Sonny R. Elizaldi: UC Davis
Jamin W. Roh: UC Davis
Brian A. Schmidt: UC Davis
Timothy D. Carroll: UC Davis
Kourtney D. Weaver: Louisiana State University Health Sciences Center
Justin C. Smith: Louisiana State University Health Sciences Center
Anil Verma: UC Davis
Jesse D. Deere: UC Davis
Joseph Dutra: UC Davis
Mars Stone: University of California
Sergej Franz: Vitalant Research Institute
Rebecca Lee Sammak: UC Davis
Katherine J. Olstad: UC Davis
J. Rachel Reader: UC Davis
Zhong-Min Ma: UC Davis
Nancy K. Nguyen: UC Davis
Jennifer Watanabe: UC Davis
Jodie Usachenko: UC Davis
Ramya Immareddy: UC Davis
JoAnn L. Yee: UC Davis
Daniela Weiskopf: La Jolla Institute for Immunology
Alessandro Sette: La Jolla Institute for Immunology
Dennis Hartigan-O’Connor: UC Davis
Stephen J. McSorley: UC Davis
John H. Morrison: UC Davis
Nam K. Tran: UC Davis
Graham Simmons: University of California
Michael P. Busch: University of California
Pamela A. Kozlowski: Louisiana State University Health Sciences Center
Koen K. A. Rompay: UC Davis
Christopher J. Miller: UC Davis
Smita S. Iyer: UC Davis

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-020-20642-x

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