The focus of this Center is immunocontraception in which the target is surface molecules of the sperm cell. Immunocontraception directed against the gamete surface is the most sophisticated barrier method of contraception, where the barrier is at the molecular level. Remarkable advances have occurred recently in immunology, molecular biology and fertilization research. These advances have combined to open possibilities for immunocontraception that were previously imagined but unattainable. Project #1 (Primakoff) proposes to develop a birth control vaccine for women which blocks fertilization and is effective, safe and widely acceptable. The vaccine uses the sperm surface protein PH-20, the only sperm protein shown to give 100% effective contraception in female animal model. Project #2 (Myles) proposes two novel strategies for development of male immunocontraceptives. The first strategy uses a vaccine based on a single epitope of the PH-30 protein. This epitope is required in fertilization and is present on epididymal but not testicular sperm. The second strategy, passive immunization, involves sustained release of monoclonal antibodies in the male which recognize either PH-20 or PH-30, sperm proteins required for fertilization. Project #3 (Bigazzi) proposes another comprehensive strategy for a male vaccine. In this case, male mice and monkeys will be immunized with PH-20 or peptides from PH-20. The immunization protocols, adjuvants and peptides will be screened to find those that induce infertility an avoid inflammation in the testis. Project #4 (Bleil) proposes the isolation of a unique type of immunocontraceptive monoclonal antibody (Mab). The Mab will inactivate sperm in the female reproductive trace by inducing a premature acrosome reaction. Project #5 (Saling) is based on Saling's discovery of a sperm plasma membrane tyrosine kinase, p95, that has properties of a receptor for ZP3. Saling proposes to clone cDNAs for mouse and human p95 and test them as contraceptive immunogens in mice and primates. Project #6 (Langer) is focused on a sustained release device for antigens that vies long-term, high titer immunization, the ideal features for a contraceptive vaccine. The further refinement of the polymeric release device developed by Langer and its application to contraceptive vaccines is proposed.
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