Immunocontraceptive vaccine development using zona pellucida (ZP)

The zona pellucida (ZP) is an extracellular matrix surrounding ovarian oocytes, ovulated eggs and preimplantation embryos. Its constituent glycoproteins are expressed in a tissue-specific manner. Since the 1970s, ZP had been assumed to be a promising candidate for immunocontraceptive vaccines, because anti-ZP antibody blocked fertilization by prevention of sperm binding to ZP in vitro. Biochemical and immunological studies revealed that ZP is composed of glycoproteins and possesses strong antigenicity. It was thus considered that ZP could surely satisfy the requirements for effective contraceptive vaccines. Contraceptive vaccines for human use should be highly effective and reversible as well as safe. However, early animal experiments showed that infertility by ZP immunization resulted from ovarian impairment. Use of immunocontraceptive vaccines with naturally occurring ZP protein has thus been limited to wildlife population control. Application of recombinant ZP proteins was expected to provide safe and irreversible vaccines but ovarian pathology could not be avoided. As a next stage, contraceptive vaccine development continued through DNA engineering, whereby the antigens were not necessarily based on native amino acid sequences of ZP. Artificial DNA constructs coding multiple promising peptides were also prepared with GnRH and promiscuous T-cell epitopes. However, their efficacy was insufficient. Recently, single chain fragment for variable regions (scFv) has been proposed as a future strategy. The scFv is expected to bind directly to ZP in the inoculated animals by skipping the antibody production process. In conclusion, intensive studies and advances in technology have not achieved ideal targets for ZP-based immunocontraceptive vaccines at this moment. We are anticipating future scientific progress.