CD4+ T cells from COVID-19 mRNA vaccine recipients recognize a conserved epitope present in diverse coronaviruses

J Clin Invest. 2022 Mar 1;132(5):e156083. doi: 10.1172/JCI156083.


Recent studies have shown that vaccinated individuals harbor T cells that can cross-recognize SARS-CoV-2 and endemic human common cold coronaviruses. However, it is still unknown whether CD4+ T cells from vaccinated individuals recognize peptides from bat coronaviruses that may have the potential of causing future pandemics. In this study, we identified a SARS-CoV-2 spike protein epitope (S815-827) that is conserved in coronaviruses from different genera and subgenera, including SARS-CoV, MERS-CoV, multiple bat coronaviruses, and a feline coronavirus. Our results showed that S815-827 was recognized by 42% of vaccinated participants in our study who received the Pfizer-BioNTech (BNT162b2) or Moderna (mRNA-1273) COVID-19 vaccines. Using T cell expansion and T cell receptor sequencing assays, we demonstrated that S815-827-reactive CD4+ T cells from the majority of responders cross-recognized homologous peptides from at least 6 other diverse coronaviruses. Our results support the hypothesis that the current mRNA vaccines elicit T cell responses that can cross-recognize bat coronaviruses and thus might induce some protection against potential zoonotic outbreaks. Furthermore, our data provide important insights that inform the development of T cell-based pan-coronavirus vaccine strategies.

Keywords: Adaptive immunity; COVID-19.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • 2019-nCoV Vaccine mRNA-1273 / administration & dosage
  • 2019-nCoV Vaccine mRNA-1273 / immunology*
  • BNT162 Vaccine / administration & dosage
  • BNT162 Vaccine / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • COVID-19 / immunology*
  • COVID-19 / prevention & control
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • Humans
  • Male
  • Peptides / immunology
  • Receptors, Antigen, T-Cell / immunology*
  • SARS-CoV-2 / immunology*
  • Spike Glycoprotein, Coronavirus / immunology*


  • Epitopes, T-Lymphocyte
  • Peptides
  • Receptors, Antigen, T-Cell
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • 2019-nCoV Vaccine mRNA-1273
  • BNT162 Vaccine