title: Gene expression and mucosal immune responses after vaginal DNA immunization in mice using a controlled delivery matrix.
abstract: IgA antibodies in the vaginal tract are essential as a first defense line against microorganisms that enter the body via mucosal surfaces. Several studies have shown that direct application of DNA to the vaginal mucosal surface can induce secretion of IgA molecules specific to the expressed protein. The major challenge of formulating effective vaccines is to overcome the barriers to DNA administration caused by the estrus cycle and physical environment of the vaginal tract. In this study, we investigated whether controlled delivery of DNA to the vaginal surface would induce long-term IgA antibody production by applying controlled delivery matrices to the vaginal tract. The controlled DNA delivery matrices were composed of poly(ethylene-co-vinyl acetate) (EVAc) and loaded with a model plasmid encoding sperm-specific lactate dehydrogenase C(4) (LDH-C(4)). These EVAc matrices provided a controlled and sustained DNA release to the vaginal mucosal surface. The DNA released from the EVAc disks was functionally active and capable of transfecting vaginal tissues. When inserted into the vaginal tract of mice, the DNA-loaded EVAc matrices triggered the immune system and induced specific IgA to LDH-C(4) in the vaginal secretions. These results demonstrate that the EVAc disks are efficient and convenient vehicles for delivering DNA to the vaginal tract and providing long-term local immunity.
authors.affiliation: School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Shen
authors.forename: Erwin
authors.initials: E
authors.lastname: Goldberg
authors.forename: W Mark
authors.initials: WM
authors.lastname: Saltzman
mesh_terms: D000282:Administration, Intravaginal; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004247:DNA / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D018928:Immunity, Mucosal / Q000187:drug effects / Q000502:physiology*; D007114:Immunization / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D014621:Vagina / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
chemical_list: D003692:Delayed-Action Preparations; D004247:DNA