Progress in the Development of Human Chorionic Gonadotropin Antifertility Vaccines

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Abstract
Prototype human chorionic gonadotropin (hCG) vaccines have demonstrated the feasibility of effectively eliciting antibodies in women and inhibiting fertility in both humans and nonhuman primates. Also, no serious side-effects due to immunization against self antigens have been revealed to date. However, the formulations so far tested in clinical trials are not suitable for widespread applications due to problems associated with complexities in production, burdensome application procedures, the need for frequent booster immunizations or cost of manufacture. Current research efforts involve the development of delivery systems to permit annual or biannual intervals between immunizations for protection from pregnancy, procedures for mucosal immunizations, methods to reduce hypersensitivity and local reactions, and procedures for reducing the cost of production. Recent progress in understanding the crystalline structure of the hCG molecule has stimulated further studies to define immunological epitope sequences that might constitute immunogens in future vaccines. The incorporation of vaccine components into biodegradable microspheres has resulted in formulations that elicit elevated antibody levels in rabbits for more than one year. Preclinical and clinical studies with such formulations are planned. Studies using totally synthetic peptide immunogens constituting hCG B-cell epitopes and "promiscuous" T-cell epitopes from bacterial or viral proteins have been shown to be equally immunogenic as conjugates of hCG peptides with macromolecular carriers. Still other peptide immunogens have been developed that can elicit antibody production without detectable proliferation of helper T cells. Some of these peptides can induce systemic immunity from oral immunization or systemic injections. Alternative vehicles for administering vaccine components with reduced local reactivity show promise for new vaccine formulations.