It has been widely hoped that immunological methods of fertility regulation by active immunization against specific antigens of the oocyte, sperm, zygote and early embryo, and the placental pregnancy hormone human chorionic gonadotropin (hCG), will provide a means to control the problem of worldwide population growth. The most advanced candidate vaccines are based on hCG immunogens and have entered clinical trials. However, during the past few years, increasing evidence has emerged that the current approaches using hCG as the target molecule may have some major drawbacks. On the basis of their recent findings, Stephan Dirnhofer and colleagues raise doubts on the suitability, safety and efficacy of gonadotropin-based immunological contraceptive vaccines.
PIP: The most advanced candidate contraceptive vaccine is based on human chorionic gonadotropin (hCG) immunogens. WHO's Task Force on Vaccines for Fertility Regulation, the National Institute of Immunology in India, and the Population Council have all developed hCG-based immunogenic formulations and have begun clinical trials. The likely mechanism of action of the hCG-based vaccine is interference with the hormone-receptor interaction, which causes reduction in the function of the corpus luteum and expulsion of the perimplantation blastocyst. The abortifacient approach of the hCG based contraceptive vaccine limits its application in many parts of the world. Other possible immunological targets could include sperm or zona pellucida membrane-associated antigens which appear to be reproduction specific and restricted to the intended target. Further, sperm antigens are not always present in the vaccine recipient. Candidate molecules should be part of the functional processes (i.e., sperm activation, adhesion between sperm and zona pellucida, and sperm-oocyte fusion). Specific immunological interception at these early reproductive event-sites would prevent conception rather than interfere with pregnancy. There are major limitations of hCG-based vaccines. For example, the biologically active domains of luteinizing hormone and hCG are quite similar, so these vaccine immunogens pose an obstacle in terms of immunological cross-reactivity. At least 3 different hCG-beta epitopes on hCG-beta core domains and on hCG-beta C-terminal peptide are accessible for antibody binding on receptor-bound hCG, which may cause an autoimmune attack against cells bearing hCG receptors in the ovary, a hazardous side effect. Various concerns about the efficacy of the hCG-based contraceptive vaccine exist.