There is an ultimate need for efficacious
vaccines against human cytomegalovirus (HCMV), which causes severe morbidity and mortality among neonates and immunocompromised individuals. In this study we explored synthetic long
peptide (SLP) vaccination as a platform modality to protect against mouse CMV (MCMV)
infection in preclinical mouse models. In both C57BL/6 and BALB/c mouse strains, prime-booster vaccination with SLPs containing MHC class I restricted
epitopes of MCMV resulted in the induction of strong and polyfunctional (i.e., IFN-γ+, TNF+, IL-2+) CD8+ T cell responses, equivalent in magnitude to those induced by the virus itself. SLP vaccination initially led to the formation of effector CD8+ T cells (KLRG1hi, CD44hi, CD127lo, CD62Llo), which eventually converted to a mixed central and effector-memory T cell phenotype. Markedly, the magnitude of the SLP
vaccine-induced CD8+ T cell response was unrelated to the T cell functional avidity but correlated to the naive CD8+ T cell precursor frequency of each
epitope. Vaccination with single SLPs displayed various levels of long-term protection against acute MCMV
infection, but superior protection occurred after vaccination with a combination of SLPs. This finding underlines the importance of the breadth of the
vaccine-induced CD8+ T cell response. Thus, SLP-based
vaccines could be a potential strategy to prevent CMV-associated disease.