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

• DOI: 10.1038/s41467-020-20642-x
• Publication Date: 2021-01-22T11:40:00Z
• Authors: Yashavanth Shaan ...; 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...; Stephen J. McSorley; John H. Morrison; Nam K. Tran; Graham Simmons; Michael P. Busch; Pamela A. Kozlowski; Koen K. A. Van Ro...; Christopher J. Mi...; Smita S. Iyer
• Keywords: Male; 0301 basic medicine; Coronaviruses; General Physics and Astronomy; Passive; Antibodies, Viral; Immunogenicity, Vaccine; Chlorocebus aethiops; Viral; Lung; Q; Humoral; Immunogenicity; Spike Glycoprotein; 3. Good health; Infectious Diseases; Medical Microbiology; Spike Glycoprotein, Coronavirus; Female; Infection; 570; T Follicular Helper Cells; Science; Immunology; 610; General Biochemistry, Genetics and Molecular Biology; Antibodies; Article; Cell Line; Vaccine Related; 03 medical and health sciences; Animals; Coronavirus Nucleocapsid Proteins; Humans; Vero Cells; COVID-19 Serotherapy; Biomedical and Clinical Sciences; Animal; SARS-CoV-2; Prevention; Inflammatory and immune system; Immunity; Immunization, Passive; COVID-19; General Chemistry; Th1 Cells; Germinal Center; Phosphoproteins; Macaca mulatta; Immunity, Humoral; Coronavirus; Disease Models, Animal; Emerging Infectious Diseases; Good Health and Well Being; Immunoglobulin G; Disease Models; Immunization; Vaccine

AbstractCD4 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.