Purpose Influenza CD8+ T-cell epitopes are conserved amongst\ninfluenza strains and can be recognized by influenza-specific cytotoxic\nT-cells (CTLs), which can rapidly clear infected cells. An\ninfluenza peptide vaccine that elicits these CTLs would therefore\nbe an alternative to current influenza vaccines, which are not\ncross-reactive. However, peptide antigens are poorly immunogenic\ndue to lack of delivery to antigen presenting cells, and\ntherefore need additional formulation with a suitable delivery\nsystem. In this study, the potential of virosomes as a delivery\nsystem for an influenza T-cell peptide was investigated.\nMethods The conserved human HLA-A2.1 influenza T-cell epitope\nM158ââ?¬â??66 was formulated with virosomes. The immunogenicity\nand protective effect of the peptide-loaded virosomes was\nassessed in HLA-A2 transgenic mice. Delivery properties of the\nvirosomes were studied in mice and in in vitro dendritic cell cultures.\nResults Immunization of HLA-A2.1 transgenic C57BL/6 mice\nwith peptide-loaded virosomes in the presence of the adjuvant\nCpG-ODN 1826 increased the number of peptide-specific\nCTLs. Vaccination with adjuvanted peptide-loaded virosomes\nreduced weight loss in mice after heterologous influenza infection.\nAssociation with fusion-active virosomes was found to be crucial\nfor antigen uptake by dendritic cells, and subsequent induction of\nCTLs in mice.\nConclusions These results show that influenza virosomes loaded\nwith conserved influenza epitopes could be the basis of a novel\ncross-protective influenza vaccine.
Loading....