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

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.