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

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 response is an important question as we investigate vaccine options for the current pandemic. Here we report that SARS-CoV-2 infection resulted in transient accumulation of pro-inflammatory monocytes and proliferating Tfh cells with a Th1 profile in peripheral blood. CD4 helper cell responses were skewed predominantly toward a Th1 response in blood, lung, and lymph nodes. We 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. 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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SARS-CoV-2 induces robust germinal center CD4 T follicular helper cell responses in rhesus macaques

Nature Communications ◽

10.1038/s41467-020-20642-x ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Yashavanth Shaan Lakshmanappa ◽

Sonny R. Elizaldi ◽

Jamin W. Roh ◽

Brian A. Schmidt ◽

Timothy D. Carroll ◽

...

Keyword(s):

Germinal Center ◽

Viral Infections ◽

Rhesus Macaques ◽

Helper Cell ◽

Nucleocapsid Proteins ◽

Cell Responses ◽

Inflammatory Monocytes ◽

Follicular Helper ◽

T Follicular Helper Cell ◽

Induced Immunity

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.

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

10.1101/2020.07.07.191007 ◽

2020 ◽

Author(s):

Sonny R. Elizaldi ◽

Yashavanth Shaan Lakshmanappa ◽

Jamin W. Roh ◽

Brian A. Schmidt ◽

Timothy D. Carroll ◽

...

Keyword(s):

Germinal Center ◽

Protective Immunity ◽

Viral Infections ◽

Rhesus Macaques ◽

Igg Antibodies ◽

Cell Responses ◽

Follicular Helper ◽

Early Appearance ◽

Iga Antibodies ◽

Stimulation Of

ABSTRACTCD4 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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