A ZONA-PELLUCIDA-3 PEPTIDE VACCINE INDUCES ANTIBODIES AND REVERSIBLE INFERTILITY WITHOUT OVARIAN PATHOLOGY

Zona pellucida 3 (ZP3) is a major glycoprotein of the zona pellucida t hat possesses the sperm receptor function. ZP3 induces autoantibody th at can block sperm/oocyte interaction. However, the feasibility of a Z P3 contraceptive vaccine has been marred by the finding that ZP3-speci fic T cells mediate ovarian autoimmune disease. Moreover, as reported in this work, only some inbred mouse strains respond to the ZP3 peptid e. We now describe a chimeric peptide that induces Abs to native ZP3 r egardless of the MHC haplotype of the inbred mice tested. Study in one mouse strain resulted in reduction in fertility that correlates well with zona pellucida Ab titer, and most importantly, the mice do not de velop concomitant autoimmune oophoritis. Moreover, the infertility was completely reversible. The design of the vaccine chimeric peptide is governed by the inclusion of two essential components: 1) a promiscuou s foreign T cell peptide capable of eliciting a Th cell response regar dless of the MHC haplotype of the animals, and 2) the native B cell pe ptide of ZP3 that has been modified by substitution of residue(s) crit ical for T cell but not B cell response to ZP3.