SARS-CoV-2 mRNA vaccines induce broad CD4+ T cell responses that recognize SARS-CoV-2 variants and HCoV-NL63

J Clin Invest. 2021 May 17;131(10):e149335. doi: 10.1172/JCI149335.


Recent studies have shown T cell cross-recognition of SARS-CoV-2 and common cold coronavirus spike proteins. However, the effect of SARS-CoV-2 vaccines on T cell responses to common cold coronaviruses (CCCs) remains unknown. In this study, we analyzed CD4+ T cell responses to spike peptides from SARS-CoV-2 and 3 CCCs (HCoV-229E, HCoV-NL63, and HCoV-OC43) before and after study participants received Pfizer-BioNTech (BNT162b2) or Moderna (mRNA-1273) mRNA-based COVID-19 vaccines. Vaccine recipients showed broad T cell responses to the SARS-CoV-2 spike protein, and we identified 23 distinct targeted peptides in 9 participants, including 1 peptide that was targeted in 6 individuals. Only 4 of these 23 targeted peptides would potentially be affected by mutations in the UK (B.1.1.7) and South African (B.1.351) variants, and CD4+ T cells from vaccine recipients recognized the 2 variant spike proteins as effectively as they recognized the spike protein from the ancestral virus. Interestingly, we observed a 3-fold increase in the CD4+ T cell responses to HCoV-NL63 spike peptides after vaccination. Our results suggest that T cell responses elicited or enhanced by SARS-CoV-2 mRNA vaccines may be able to control SARS-CoV-2 variants and lead to cross-protection against some endemic coronaviruses.

Keywords: COVID-19; T cells.

Publication types

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

MeSH terms

  • Adult
  • BNT162 Vaccine
  • CD4-Positive T-Lymphocytes / immunology*
  • COVID-19 Vaccines / immunology*
  • Coronavirus 229E, Human* / genetics
  • Coronavirus 229E, Human* / immunology
  • Coronavirus NL63, Human* / genetics
  • Coronavirus NL63, Human* / immunology
  • Coronavirus OC43, Human* / genetics
  • Coronavirus OC43, Human* / immunology
  • Cross Reactions
  • Female
  • Humans
  • Male
  • Middle Aged
  • RNA, Messenger* / genetics
  • RNA, Messenger* / immunology
  • SARS-CoV-2* / genetics
  • SARS-CoV-2* / immunology
  • Spike Glycoprotein, Coronavirus* / genetics
  • Spike Glycoprotein, Coronavirus* / immunology


  • COVID-19 Vaccines
  • RNA, Messenger
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • BNT162 Vaccine