This proposal is designed to address the great need to enhance immune responses against microbial agents which cause sexually transmitted diseases (STDs). With diseases which are only (or primarily) transmitted sexually, enhanced immunity at the reproductive mucosa is key. We chose to study immunity at the female reproductive mucosa in trichomoniasis because a) trichomoniasis is a human STD of increasing importance, b) there is a bovine model of trichomoniasis in which immunity can be studied in the natural host and challenge infection can be done, c) we have experience with the bovine model, d) bovine trichomoniasis is one of the few STDs which can be controlled by vaccination. For these reasons, we will use the bovine trichomoniasis model to develop means to enhance mucosal immunity to a defined protective antigen. To accomplish this goal, our objectives are to: 1) immunize mice with purified trichomonad protective antigen TF1.17 mixed with alum, or Quil A adjuvants or conjugated to cholera toxin (CT) adjuvant. Intravaginal or subcutaneous routes will be used. IgG and IgA vaginal or serum antibodies to TF1.17 antigen will be quantitated by ELISA. 2) determine whether a better local immune response results after intravaginal administration of antigen/adjuvant with or without a foam delivery system in mice. 3) compare serum and vaginal antibody responses of cattle to TF1.17 antigen after vaginal immunization with adjuvants from above studies. 4) assess protection of cattle against trichomoniasis with TF1.17 antigen immunization using the best local and systemic vaccination formulations from the above studies. 5) investigate antigenic variation of weekly trichomonad isolates from the bovine challenge experiment (AIM 4). 6) compare vaginal and systemic isotypic antibody titers with protection in locally immunized, systemically immunized, and control cattle. 7) determine functions of IgA vs. IgG antibodies from vaginal secretions. 8) compare isotypic antibody responses in the uterus and vagina for each group of cattle with day of clearance of the organism and with stage of the estrus cycle. 9) determine relationships between enhanced immunogenicity and degree of inflammation in the vagina, cervix, uterus and oviducts of immunized and control cattle. These studies are expected to show which adjuvant (or antigen-adjuvant conjugates), routes and delivery systems enhance genital mucosal immunity resulting in enhanced protection against an important STD. The results should have broad significance since vaccines are unavailable to protect against human diseases which are primarily transmitted sexually.
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