ABSTRACT
CD4 T follicular helper (T fh ) 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 T fh 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 T fh cells in their peripheral blood on a transitory basis. The CD4 helper cell responses were skewed predominantly toward a T h 1 response in blood, lung, and lymph nodes, reflective of the interferon-rich cytokine environment following infection. We also observed the generation of germinal center T fh 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.
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.
Subject(s)
COVID-19/immunology , Germinal Center/immunology , SARS-CoV-2/immunology , T Follicular Helper Cells/immunology , Th1 Cells/immunology , Animals , Antibodies, Viral/blood , COVID-19/therapy , Cell Line , Chlorocebus aethiops , Coronavirus Nucleocapsid Proteins/immunology , Disease Models, Animal , Female , Humans , Immunity, Humoral/immunology , Immunization, Passive , Immunogenicity, Vaccine/immunology , Immunoglobulin G/blood , Macaca mulatta , Male , Phosphoproteins/immunology , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/immunology , Vero Cells , COVID-19 SerotherapyABSTRACT
CD4 T follicular helper (T fh ) 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 T fh 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 T fh cells in their peripheral blood on a transitory basis. The CD4 helper cell responses were skewed predominantly toward a T h 1 response in blood, lung, and lymph nodes, reflective of the interferon-rich cytokine environment following infection. We also observed the generation of germinal center T fh 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.