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 remain unknown. In this study, we analyzed CD4+ T cell responses to spike peptides from SARS-CoV-2 and 3 common cold coronaviruses (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 made broad T cell responses to the SARS-CoV-2 spike protein and we identified 23 distinct targeted peptides in 9 participants including one peptide that was targeted by 6 individuals. Only 4 out 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 the spike protein from the ancestral virus. Interestingly, we saw a 3-fold increase in the CD4+ T cell responses to HCoV-NL63 spike peptides post-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 from some endemic coronaviruses.

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