Intranasal immunization with plasmid DNA-Lipid complexes elicits mucosal immunity in the female genital and rectal tracts

The development of vaccines against pathogens transmitted across the genito -rectal mucosa that effectively stimulate both secretory IgA Abs and cytoto xic T lymphocytes in the genital tract and CTL in the draining lymph nodes (LN) has proven a major challenge. Here we report a novel, noninvasive appr oach of genetic vaccination via the intranasal route. Such vaccination elic its immune responses in the genital and rectal mucosa, draining LNs, and ce ntral lymphoid system, Intranasal immunization with plasmid DNA-lipid compl exes encoding the model Ag firefly luciferase resulted in dissemination of the DNA and the encoded transcript throughout the respiratory and gastroint estinal tracts, draining LNs, and spleen. Complexing the plasmid DNA with t he lipid DMRIE/DOPE enhanced expression of the encoded protein in the respi ratory tract, increased specific secretory IgA Ab in the vaginal and rectal tracts, and increased the circulating levels of specific IgA and IgG. In a ddition, intranasal DNA immunization resulted in generation of Ag-specific CTL that were localized in the genital and cervical LNs and spleen. These r esults suggest that intranasal immunization with plasmid DNA-lipid complexe s may represent a generic immunization strategy against pathogens transmitt ed across the genito-rectal and other mucosal surfaces.