Typically immunocontraception involves the administration of a vaccine that induces an adaptive immune response which causes an animal to become temporarily infertile.
[1] However, experts in the field believe that major innovations are required before immunocontraception can become a practical form of contraception for human beings.
[8] 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.
[10] 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.
[14] One concern with zona pellucida vaccination, in particular, is that in certain cases it appears to be correlated with ovarian pathogenesis.
GnRH is secreted by the hypothalamus in pulses and travels to the anterior pituitary gland through a portal venous system.
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.
[4] Improvac® is a GnRH vaccine marketed for use in pigs not as a contraceptive, but as an alternative to physical castration for the control of boar taint.
[5] Unlike the other products which are marketed for use in domestic animals, GonaCon™ is a GnRH vaccine being developed as a United States Department of Agriculture initiative for use for control of wildlife, specifically deer.
[19] Work begun by researchers at the University of Tennessee in the 1970s into immunity against zonae pellucidae resulted in its identification as a target antigen for immunocontraception.
[20] In 1987, a pharmaceutical company called Zonagen (later renamed Repros Therapeutics) was started with the goal of developing zona pellucida vaccines as an alternative to the surgical sterilization of companion animals and eventually as a contraceptive for human use.
[21] Also in the late 1980s, research began into the use of vaccines based around zonae pellucidae harvested from pigs for the purpose of wildlife control.
Such porcine zona pellucida (PZP) vaccines were tested in captive and domestic horses in 1986 with encouraging results.
[1] In 2012, researchers from Brawijaya University in conjunction with pharmaceutical company Bio Farma received a grant from the Indonesian government to develop a zona pellucida contraceptive vaccine for human use.
Research in these countries has therefore focused on genetically modifying viruses or microorganisms that infect the unwanted invasive species to contain immunocontraceptive antigens.
[36] Initial exploration into the control of the common brushtail possum (Trichosurus vulpecula) in New Zealand using the nematode Parastrongyloides trichosuri has identified it as a possible immunocontraceptive vector.
[8] In 1899, the discovery of the existence of antibodies against sperm was made independently both by Serge Metchnikoff[38] of the Pasteur Institute and by Nobel prize laureate Karl Landsteiner.
[39] In 1929, the first recorded attempt at immunocontraception was made by Morris Baskin, clinical director of the Denver Maternal Hygiene Committee.
In this trial 20 women who were known to have at least 1 prior pregnancy were injected with their husband's semen, and no conception was recorded in 1 year of observation of these couples.
One study examined the sperm-specific isozyme of human lactate dehydrogenase (LDH-C4) combined with a T-cell epitope to create a synthetic peptide that acted as a more potent chimeric antigen.
[59] However, a second study that examined vaccination of female macaque monkeys with the same synthetic peptide did not find reduced fertility.
[60] Finally, while there has been autoimmune ovarian pathogenesis found in some trials using zona pellucida vaccines,[2] anti-sperm antibodies are not likely to have adverse health effects, since anti-sperm antibodies are produced by up to 70% of men who have had vasectomies, and there has been much investigation into possible adverse health side-effects of the vasectomy procedure.
[61] A vaccine induces active immunity when antigens are injected into an animal that cause it to produce desired antibodies itself.
[64] Research done using phage display technology on lymphocytes from immunoinfertile men led to the isolation, characterization, and synthesis of specific antibodies that inhibit fertility by acting against several of the known sperm antigens.
[8] Most of the research into immunity that inhibits gamete outcome has focused on human chorionic gonadotropin (hCG).
[6] The main function of hCG is to sustain the ovarian corpus luteum during pregnancy past the time it would normally decay as part of the regular menstrual cycle.
[69] This was followed by another phase I trial in 1977-1978 examining previously sterilized women at 5 institutions in India with a more potent vaccine that combined the beta subunit of hCG with the alpha subunit of ovine luteinizing hormone to form a heterospecies dimer conjugated with both tetanus toxoid and diphtheria toxoid.
Blood samples were taken twice a month, and booster injections were given when antibody titers declined below 50 ng/mL in women who wished to continue using the vaccine.
It has been approved by the Indian National Review Committee on Genetic Manipulation and is being produced for pre-clinical toxicology testing.
[83][84][85] Field trials of immunocontraception in wildlife, on the other hand, established that contraceptive vaccines could be delivered remotely by capture gun, were safe to use in pregnant animals, were reversible, and induced long-lasting infertility, overcoming these practical limitations.