T cell immunity of the nonadjuvanted HLA-restricted peptide COVID-19 vaccine

Abstract Recently, the cases of breakthrough infection and restored virus of COVID-19 have increased after full vaccination, which might be contributed by immune surveillance escape or rebound virus. Here, artificial linear 9-mer human leucocyte antigen (HLA)-restricted UC peptides are designed based on the well-conserved S2 region of the COVID-19 spike protein regardless of rapid mutation and glycosylation hindrance. Through HLA molecule presentation, UC peptides can activate cytotoxic T lymphocytes (CTLs), which elicit cytotoxic activity by recognizing COVID-19 spike-bearing cells and preferably secreting Th1 cytokines. The UC peptides showed immunogenicity and generated a specific antibody in mice either by intramuscular injection or oral delivery without an adjuvant formulation. In conclusion, the T cell vaccine could provide long-lasting protection against COVID-19 either during reinfection or during the rebound of COVID-19. With the eradication of COVID-19 virus-infected cells, the COVID-19 T cell vaccine might provide a solution to lower COVID-19 severity and long COVID.