The primary goal of this research proposal is to develop an oral contraceptive vaccine and to study the ability of this oral vaccine to induce infertility and secretory immunity within the female reproductive tract. The oral recombinant contraceptive vaccine to be developed will consist of avirulent strains of Salmonella which will be genetically engineered to express the human sperm immunogen SP-10. The avirulent strains of Salmonella will induce immunity by stimulating the gut associated lymphoid tissues [GALT] to dispel populations of specific antibody secreting cells which will populate the female reproductive organs. Experiments will be conducted on the cynomolgus monkey, Macca fascicularis. During the initial phase of the work the SP-10 immunogen will be engineered into avirulent strains of Salmonella and the stability and immunogenicity of the constructs evaluated in mice. In parallel with this goal, methods will be developed to measure specific antibody concentrations in the fluids and mucus of macaque ovarian follicles, oviducts, uterus and cervix and to determine the numbers and location of specific antibody secreting cells arising in these organs and in the circulation following parenteral immunization. Having developed methods of measuring immune responses in the monkey female tract, the effect of the oral contraceptive vaccine on secretory immunity within the ovaries, oviducts, uterus, cervix and circulation will be evaluated in monkeys. Most importantly, the anti-fertility potential of the oral contraceptive vaccine will be evaluated. Infertility will be correlated with levels of serum antibody as well as the degree to which secretory immunity was induced within the female tract. Finally, antibodies to SP-10 from serum and reproductive tract secretions will be studied for their ability to inhibit monkey in vitro fertilization. Using affinity purified antibodies, the precise stoichiometry of immunoglobulin required for inhibitory effects will be determined and these amounts compared to antibody levels induced within follicular, oviductal and cervical secretions by oral immunization. The sperm based recombinant oral contraceptive vaccine to be developed in this program will provide fundamental information on oviductal secretory immunity with wide application as a model for understanding contraceptive vaccine action.
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