title: Vaccine delivery by polymeric vehicles in the mouse reproductive tract induces sustained local and systemic immunity.
abstract: Design of easily administered vaccines to protect the female reproductive tract against STIs such as HIV, HPV and HSV is a major step in improving world health standards. However, the effect of immunization routes and regimens (prime/boost) on immune response is not well-understood. Here, we present a systematic study of vaccine delivery by different routes and prime/boosting regimens to produce a robust humoral immune response in the reproductive tract. A model antigen, ovalbumin (OVA), was delivered orally or intranasally via polymer particles, and intravaginally via polymer disks to female mice. Repeated prime/boost at a single site result in high OVA-specific antibody levels in the serum for mice immunized orally (IgA) and invaginally (IgA and IgG) after 3 months. Vaginal antibody titers were the highest for mice immunized by intravaginal routes. Vaginal boosting following intranasal or oral priming did not appear to offer similar advantages to those primed intravaginally. Systemic immunization with OVA in Freund's adjuvant produced robust serum IgG levels, but little serum IgA or antibodies in the vaginal washings. All immunization schemes produced a significant level of IgG in the intestinal mucosa, with the exception of nasal priming followed by intravaginal boost with slow-releasing disks. In contrast, only immunization by nasal priming and intravaginal boost with fast-releasing disks was able to achieve significantly high intestinal IgA titers.
authors.affiliation: Department of Chemical Engineering, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Kuo-Haller
authors.forename: Yen
authors.initials: Y
authors.lastname: Cu
authors.forename: Jeremy
authors.initials: J
authors.lastname: Blum
authors.forename: Judith A
authors.initials: JA
authors.lastname: Appleton
authors.forename: W Mark
authors.initials: WM
authors.lastname: Saltzman
mesh_terms: D000282:Administration, Intravaginal; D000284:Administration, Oral; D000818:Animals; D000918:Antibody Specificity; D016503:Drug Delivery Systems; D005260:Female; D018928:Immunity, Mucosal; D007117:Immunization, Secondary / Q000379:methods; D007070:Immunoglobulin A / Q000097:blood / Q000378:metabolism; D007074:Immunoglobulin G / Q000097:blood / Q000378:metabolism; D019344:Lactic Acid; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D018448:Models, Immunological; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D014612:Vaccines / Q000008:administration & dosage*; D014621:Vagina / Q000276:immunology
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G; D014612:Vaccines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D010047:Ovalbumin