Contraceptive vaccines

Abstract

Three major approaches to contraceptive vaccine development are being pursued at the present time. The most advanced approach, which has already reached the stage of phase 2 clinical trials, involves the induction of immunity against human chorionic gonadotrophin (hCG). Vaccines are being engineered based on conjugates incorporating tetanus or diphtheria toxoid linked to a variety of hCG-based peptides centred on the beta-subunit of this molecule. Clinical trials have revealed that such preparations are capable of stimulating the production of anti-hCG antibodies. However, the long term consequences of such immunity in terms of safety or efficacy are, as yet, unknown. The alternative approaches to contraceptive vaccine development involve the induction of immunity against gamete-specific antigens found on the surface of the human spermatozoon or the zona pellucida. There is an abundance of experimental and clinical data to suggest that this approach is feasible although the biochemical characterization and synthesis of candidate antigens is still incomplete.

PIP: The 3 primary candidates for the development of a contraceptive vaccine are: a) human chorionic gonadotropin (hCG), b) the zona pellucida, and c) the sperm surface. The most advanced approach involves the induction of immunity against hCG. Completed Phase I clinical trials have revealed that such preparations are capable of stimulating the production of anti-hCG antibodies. Phase 2 studies are about to commence. Vaccines are being engineered based on conjugates which incorporate tetanus or diphtheria toxoid linked to a variety of hCG-based peptides centered on the beta-subunit of this molecule. However, the longterm safety of efficacy of such immunity is unknown. The remaining 2 vaccine development approaches aim to prevent conception by interfering with the interactive events that characterize the union of male and female gametes of fertilization. The zona glycoprotein, ZP3, is a prime candidate for such a vaccine, in the view of its important role in the recognition and activation of spermatozoa and its unique antigenic composition. A major problem with this approach involves the loss of primordial follicles observed in the many in vivo studies in which active immunity against this protein has been induced. The possibility that this problem can be overcome by identifying B-cell epitopes that will avoid the T-cell responses thought to be responsible for the appearance of ovarian dysfunction is now being actively investigated. Disruption of fertilization through the induction of immunity against sperm surface antigens is a third approach, for which there is clinical support as patients have exhibited infertility associated with the appearance of spontaneous immunity against sperm antigens. Potential targets are constrained by considerations of immunogenicity, specificity, antigen density, and location.