Purpose: Influenza CD8(+) T-cell epitopes are conserved amongst influenza strains and can be recognized by influenza-specific cytotoxic T-cells (CTLs), which can rapidly clear infected cells. An influenza peptide vaccine that elicits these CTLs would therefore be an alternative to current influenza vaccines, which are not cross-reactive. However, peptide antigens are poorly immunogenic due to lack of delivery to antigen presenting cells, and therefore need additional formulation with a suitable delivery system. In this study, the potential of virosomes as a delivery system for an influenza T-cell peptide was investigated.
Methods: The conserved human HLA-A2.1 influenza T-cell epitope M158-66 was formulated with virosomes. The immunogenicity and protective effect of the peptide-loaded virosomes was assessed in HLA-A2 transgenic mice. Delivery properties of the virosomes were studied in mice and in in vitro dendritic cell cultures.
Results: Immunization of HLA-A2.1 transgenic C57BL/6 mice with peptide-loaded virosomes in the presence of the adjuvant CpG-ODN 1826 increased the number of peptide-specific CTLs. Vaccination with adjuvanted peptide-loaded virosomes reduced weight loss in mice after heterologous influenza infection. Association with fusion-active virosomes was found to be crucial for antigen uptake by dendritic cells, and subsequent induction of CTLs in mice.
Conclusions: These results show that influenza virosomes loaded with conserved influenza epitopes could be the basis of a novel cross-protective influenza vaccine.