Local gene expression and immune responses of vaginal DNA vaccination using a needle-free injector.
The vaginal mucosa is the most common site of initiation of virus infections that are transmitted through heterosexual intercourse, including HIV and papillomavirus. Thus, in order to prevent or treat these infections, strong vaginal immunity is required as the first line of defense. In this study, to establish a less invasive, safe, convenient and effective immunization method, we examined the local (skin and vagina) gene transfection efficiency of a non-needle jet injector for daily insulin injection. In the skin experiment, the needle-free injector resulted in a marked increase in marker gene expression, compared to the conventional needle-syringe injection. In addition, intradermal DNA vaccination using the needle-free injector dramatically induced IFN-gamma and antibody systemic responses in mice. Furthermore, we investigated the applicability of the needle-free injector as a vaginal vaccination tool in rabbits. Vaginal gene expression using the needle-free injector was significantly greater than that using needle-syringe injection. Moreover, intravaginal vaccination by the needle-free injector promoted vaginal IgA secretion and IFN-gamma mRNA expression in the blood lymphocytes, to a degree significantly higher than that by needle-syringe injection. In conclusion, local vaginal DNA vaccination using a needle-free jet injector is a promising approach for the prevention and treatment of mucosal infectious diseases.
Kanazawa
Takanori
T
Laboratory of Pharmaceutics and Drug Delivery, Department of Pharmaceutical Science, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Takashima
Yuuki
Y
Tamura
Toshiaki
T
Tsuchiya
Miki
M
Shibata
Yasunori
Y
Udagawa
Haruhide
H
Okada
Hiroaki
H
D000282:Administration, Intravaginal; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D018928:Immunity, Mucosal; D007074:Immunoglobulin G / Q000097:blood; D007277:Injections, Jet; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000276:immunology; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D015229:Sexually Transmitted Diseases, Viral / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D012867:Skin / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology; D014621:Vagina / Q000276:immunology*
D007074:Immunoglobulin G; D019444:Vaccines, DNA; D007371:Interferon-gamma