Contraception Immunological

GP Talwar, International Centre for Genetic Engineering and Biotechnology, New Delhi, India

A major technological advance in the twentieth century was the development of a number of methods to prevent an unwanted pregnancy. Amongst newer methods currently under development are those which employ immunological approaches. Vaccines inducing appropriate immune response have been made, with demonstrated ability to control fertility in experimental animals, including subhuman primates. Extensive safety and toxicology studies have shown the safety and reversibility of some of these vaccines, and these, with due approval of the drugs regulatory authorities and institutional ethics committees, have undergone clinical trials in humans. Six vaccines have completed phase I clinical trials documenting their safety and reversibility - three vaccines in women and three in men. One vaccine has also successfully completed the phase II trials in women, providing evidence for its efficacy in preventing preg nancy. These trials have established the titers of antibodies and other characteristics (avidity, immuno-

dominant epitopes, bioneutralization capacity) to achieve efficacy. Of interest is the application of some of these vaccines in hormone-dependent cancers (carcinoma of the prostate) and lung cancers secreting human chorionic gonadotropin (hCG).


The rationale behind birth control vaccines is the generation of antibodies and/or cell-mediated immune responses (CMIs) against either a hormone or gamete antigen(s) important for the success of reproduction. The production of the gametes in both males and females is critically regulated by hormones. A cascade of hormones is involved, starting from the gonadotropin-releasing hormone (GnRH or LHRH) secreted by the hypothalamus. This decapep-tide hormone, common to both males and females, stimulates the production and secretion of the two gonadotropins follicle stimulating hormone (FSH) and luteinizing hormone (LH) by the pituitary. These act in concert on the gonads to generate eggs or sperm from the ovaries or the testes, respectively (Figure 1).

The fertilized egg also makes the hormone hCG, secretion of which by the preimplantation human embryo is detectable in culture following in vitro fertilization prior to transfer to the uterus. Evidence points to a crucial role of this hormone in implantation, and antibodies inactivating hCG intercept implantation. Following implantation, the amount of hCG secreted increases sharply until 7-9 weeks of pregnancy, after which it declines to a lower level and stays so throughout pregnancy in humans. A second important biological role of hCG is in sustenance of the ovarian corpus luteum and in continued production of progesterone for the first 7-9 weeks, after which the placenta takes over the production of progesterone. hCG thus has a dual role, in establishment of pregnancy (implantation of the embryo into the endometrium) and in its sustenance for at least 7-9 weeks. Antibodies against hCG can prevent the establishment of the pregnancy if these are preexisting in the circulation by virtue of active immunization. Antibodies given passively at the postimplantation stage but during the first 7 weeks of pregnancy have been shown, in baboons, to terminate pregnancy and thus act as an abortifacient.

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