Immunocontraception with zone pellucida proteins

The prospect of an immunological approach to contraception that would disru pt the process of fertilisation itself has resulted in a considerable inter est into research in this area. It has been known for some time that antibo dies raised against the zona pellucida (ZP) can suppress fertility very eff ectively. However, the initial optimism of this approach has been marred by the appearance of an ovarian pathology characterised by disruption of foll iculogenesis and depletion of the primordial follicle pool. Adverse auto-im mune reactions have been observed in the ovaries of mice after the inductio n of immunity with mouse ZP3 epitopes, However, this was associated with ly mphocytic infiltration of the ovarian stroma, which could be circumvented b y careful selection of B-cell epitopes to induce reversible infertility. In order to identify similar epitopes on primate ZP3, epitope-mapping studies were performed and incorporated into chimeric vaccines that included a pro miscuous T-helper cell epitope. Both single and triple peptide vaccines hav e been evaluated in vivo and no detrimental effects on ovarian function wer e observed. The resulting high titre antibodies bound exclusively to the ZP of marmoset and human ovarian sections and could suppress in vitro human s perm-egg binding by approximately 60%, but did nor prevent pregnancy in act ively immunised female marmosets. Thus, considerable research is still requ ired to identify a combination of ZP3 epitopes that will induce infertility free of any unwanted side effects. Copyright (C) 2000 S. Karger AG, Basel.