Needle-free intravaginal DNA vaccination using a stearoyl oligopeptide carrier promotes local gene expression and immune responses

Abstract

The vaginal mucosa is the most common site of infection for viruses that are transmitted through heterosexual intercourse, including human immunodeficiency virus and papillomavirus. Thus, in order to prevent or respond to these infections, strong vaginal immunity is required as the first line of defense. We previously investigated the use of a needle-free injector as a mucosal vaccination tool in rabbits and demonstrated that this is a promising method for stimulating vaginal gene expression and immune responses. In order to improve gene expression, we have examined local vaginal gene transfection efficiency using a non-needle jet injector combined with an effective peptide carrier in rabbits. The carrier used was a stearoyl (STR) peptide with Cys (C), Arg (R) and His (H) residues that form disulfide cross linkages via Cys (STR-CH₂R₄H₂C) which was developed in our previous study. As a result, vaginal gene expression using the needle-free injector combined with STR-CH₂R₄H₂C carrier was significantly improved compared to that without STR-CH₂R₄H₂C carrier. Moreover, intravaginal pDNA vaccination by the needle-free injector combined with STR-CH₂R₄H₂C carrier and CpG-ODN promoted not only local vaginal IgA and IgG, but also serum IgG secretion, to a degree significantly higher than that of naked pDNA.