A novel dodecamer peptide sequence, YLP(12), was identified on human sperm that is involved in oocyte binding. We investigated its immunocontraceptive effects in a murine model. A vaccine was prepared by conjugating the synthetic YLP(12) peptide with the binding subunit of recombinant cholera toxin. Vaccination of female mice by i.m. or intranasal routes without any additional adjuvant induced a sperm-specific immune response in serum and the vaginal tract that caused a long-term contraceptive state. Fertility was fully regained when antibody reactivity diminished at 305-322 days. The contraceptive effect was also completely reversed voluntarily by intravaginal administration of the peptide. Antibodies affected fertility at the prefertilization stage by inhibiting sperm capacitation and the acrosome reaction, and sperm-oocyte binding. The peptide sequence is an epitope of a 50 +/- 5-kDa membrane protein localized on the acrosome and tail of spermatozoa. Thus, the sperm-specific YLP(12) is an attractive candidate for contraceptive vaccine.
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