Immunocontraception

Immunocontraception is the use of an animal's immune system to prevent it from fertilizing offspring. Contraceptives of this type are not currently available for human use. Immunocontraception is the use of an animal's immune system to prevent it from fertilizing offspring. Contraceptives of this type are not currently available for human use. Typically immunocontraception involves the administration of a vaccine that induces an adaptive immune response which causes an animal to become temporarily infertile. Contraceptive vaccines have been used in numerous settings for the control of wildlife populations. However, experts in the field believe that major innovations are required before immunocontraception can become a practical form of contraception for human beings. Thus far immunocontraception has focused on mammals exclusively. There are several targets in mammalian sexual reproduction for immune inhibition. They can be organized into three categories. Immunocontraception in not currently available but is under study. In order for an immunocontraceptive to be palatable for human use, it would need to meet or exceed the efficacy rates of currently popular forms of contraception. Currently the maximum reduction of fertility due to sperm vaccines in laboratory experiments with mice is ~75%. The lack of efficacy is due to variability of immunogenicity from one animal to another. Even when exposed to the same exact vaccine, some animals will produce abundant antibody titers to the vaccine's antigen, while others produce relatively low antibody titers. In the Eppin trial that attained 100% infertility, a small sample size (only 9 monkeys) was used, and even among this small sample 2 monkeys were dropped from the study because they failed to produce sufficiently high antibody titers. This trend—high efficacy when antibody titers are above a threshold coupled with variability in how many animals reach such a threshold—is seen throughout immunocontraception and immune-based birth control research. A long term study of PZP vaccination in deer that spanned 6 years found that infertility was directly related to antibody titers to PZP. The phase II clinical trial of hCG vaccines was quite successful among women who had antibody titers above 50 ng/mL, but quite poor among those with antibody titers below this threshold. Mucosal immunity, which includes immune function in the female reproductive tract, is not as well understood as humoral immunity. This may be an issue for certain contraceptive vaccines. For instance, in the second LDH-C4 primate trial that had negative results, all of the immunized macaque monkeys developed high antibody titers against LDH-C4 in serum, but antibodies against LDH-C4 were not found in the monkeys' vaginal fluids. If antibodies against LDH-C4 do indeed inhibit fertilization, then this result highlights how the difference in the functioning of mucosal immunity from humoral immunity may be critical to the efficacy of contraceptive vaccines. Whenever an immune response is provoked, there is some risk of autoimmunity. Therefore, immunocontraception trials typically check for signs of autoimmune disease. One concern with zona pellucida vaccination, in particular, is that in certain cases it appears to be correlated with ovarian pathogenesis. However, ovarian disease has not been observed in every trial of zona pellucida vaccination, and when observed, has not always been irreversible. The production of gametes is induced in both male and female mammals by the same two hormones: follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The production of these in turn is induced by a single releasing hormone, gonadotropin-releasing hormone (GnRH), which has been the focus of most of the research into immunocontraception against gamete production. GnRH is secreted by the hypothalamus in pulses and travels to the anterior pituitary gland through a portal venous system. There it stimulates the production of FSH and LH. FSH and LH travel through the general circulatory system and stimulate the functioning of the gonads, including the production of gametes and the secretion of sex steroid hormones. Immunity against GnRH thus lessens FSH and LH production which in turn attenuates gamete production and secondary sexual characteristics.