Novel conjugates of epitope fusion peptides with CpG-ODN display enhanced immunogenicity and HIV recognition

Vaccination strategies remain elusive that are effective against viral disease pathogens yet remain gentle enough for widespread human use. We developed a model system that relies on the recognition of specific T-cell epitopes from immunodominant antigens of HIV to explore single-stranded CpG-oligodeoxynucleotides (ODN) (CpG) as an adjuvant. We improved upon current strategies of utilizing CpG in combination with peptide vaccines by covalently modifying epitope fusion peptides with CpG motifs. Characterization of the immune recognition of DNA–peptide conjugates was carried out in a murine model of human HLA A2. Immunogenicity of DNA–peptide conjugates was superior in sensitivity to non-covalently linked mixtures of the same functional molecules as measured by peptide-mediated cytotoxicity and IFN-γ release, as well as protection against viral infection. Enhancement of sensitivity of immune recognition by covalent attachment of DNA to epitope peptides should be further evaluated as a novel prophylactic vaccine strategy for HIV infection and other infectious diseases.