Complexes of DNA vaccines with cationic, antigenic peptides are potent, polyvalent CD8(+) T-cell-stimulating immunogens.

A priority in current vaccine research is the development of multivalent vaccines that support the efficient priming of long-lasting CD8(+) T-cell immunity. We developed a novel vaccination strategy that used synthetic, cationic (positively charged), and antigenic peptides complexed to negatively charged nucleic acids: antigenic, major histocompatibility complex-class I-binding epitopes fused with a cationic sequence derived from the HIV tat protein (tat50-57: KKRRQRRR) were mixed with nucleic acids (e.g., CpG-containing oligonucleotides) to quantitatively form peptide/nucleic acid complexes. The injection of these complexes efficiently primed long-lasting, specific CD8(+) T-cell immunity of high magnitude. This chapter describes a novel strategy to codeliver complexes of cationic/antigenic peptides bound to antigen-encoding plasmid DNA vaccines in a way that enhances the immunogenicity of both components for T cells.