T-cell responses to highly conserved SARS-CoV-2 epitopes in Hispanic Americans receiving an mRNA COVID-19 vaccine

This study reports the pre-clinical evaluation of peptides from EPV-CoV-19, a T cell epitope-based SARS-CoV-2 vaccine candidate, following spike-mRNA vaccination of a predominantly Hispanic American cohort. EPV-COV-19 peptides’ potential to boost T cell responses to spike protein vaccines was evaluated, confirming previously observed memory recall responses in donors with prior immunity to COVID-19. The vaccinated subjects’ averaged immune responses to the 15-peptide EPV-CoV-19 pool achieved 85% of the observed response to a spike protein peptide array containing a 7-fold greater epitope content, suggesting that the EPV-CoV-19 peptides have a higher relative concentration of T cell epitope content per-peptide. Ten of the 15 peptides contained spike epitopes conserved in the majority of variants of concern (VOC) evaluated over the 2020–2024 period. While commercial vaccines exhibited gradual loss of T cell epitope conservation with VOC over time, the EPV-CoV-19 epitope-peptides maintained conservation until the XBB variant emerged. The addition of one new peptide to the vaccine design reestablished broad T cell epitope coverage. These findings underscore the importance of identifying highly conserved T cell epitopes for vaccine designs that target rapidly-mutating strains of emergent pathogens, while also documenting broad memory T cell response to the vaccine in a predominantly Hispanic American cohort.