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

Nat Commun. 2021 Jan 22;12(1):541. doi: 10.1038/s41467-020-20642-x.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / blood
  • COVID-19 / immunology*
  • COVID-19 / therapy
  • Cell Line
  • Chlorocebus aethiops
  • Coronavirus Nucleocapsid Proteins / immunology
  • Disease Models, Animal
  • Female
  • Germinal Center / immunology*
  • Humans
  • Immunity, Humoral / immunology
  • Immunization, Passive
  • Immunogenicity, Vaccine / immunology
  • Immunoglobulin G / blood
  • Macaca mulatta
  • Male
  • Phosphoproteins / immunology
  • SARS-CoV-2 / immunology*
  • SARS-CoV-2 / isolation & purification
  • Spike Glycoprotein, Coronavirus / immunology
  • T Follicular Helper Cells / immunology*
  • Th1 Cells / immunology*
  • Vero Cells


  • Antibodies, Viral
  • Coronavirus Nucleocapsid Proteins
  • Immunoglobulin G
  • Phosphoproteins
  • Spike Glycoprotein, Coronavirus
  • nucleocapsid phosphoprotein, SARS-CoV-2
  • spike protein, SARS-CoV-2

Supplementary concepts

  • COVID-19 serotherapy

Associated data

  • figshare/10.6084/m9.figshare.13270325