A novel contraceptive approach that is gaining substantial attention is “immunocontraception” targeting gamete production, gamete outcome, or gamete function. Amongst these, use of sperm antigens (gamete function) seems to be an exciting and feasible approach. However, the variability of immune response and time lag to attain titer among vaccinated individuals after active immunization has highlighted the potential relevance of preformed antibodies in this league. This review is an attempt to analyze the current status and progress of immunocontraceptive approaches with respect to their establishment as a future fertility control agent.
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A novel contraceptive approach that is gaining substantial attention is immunocontraception, which is the use of contraceptive vaccines (CVs) or preformed antibodies to prevent fertilization. As with the conventional vaccines, CVs utilise the body's defense system to wedge an essential step in the reproductive process [6]. A successful contraceptive vaccine must meet a number of criteria; it must be reliable, easy to administer, safe, affordable, widely acceptable, and capable of evoking homogeneous response and must bestow a high level of contraceptive efficacy.
There are three major categories involved in the development of CVs including gamete production, namely, gonadotropin releasing hormone (GnRH), follicle stimulating hormone (FSH), and luteinizing hormone (LH); gamete outcome, namely, human chorionic gonadotropin (hCG), or gamete function, namely, zona pellucida (ZP) and sperm antigens [7]. Of all, validation and practicability for the development of antisperm vaccines targeting prefertilization events seem to be much more encouraging and promising.
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When GnRH vaccine was tested on human subjects, including breastfeeding women by The National Institute of Immunology, India, and the Population Control Council, USA, the vaccine essentially resulted in castration and halted testosterone production [11]. However, these results were accompanied with impotence and loss of body hair in case of men and affected menopause in women [12]. Hence, an analogue of GnRH was prepared by linking with different carriers in an attempt to make improved vaccine [7].
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Immunization of male bonnet monkeys with ovine FSH resulted in testicular dysfunction, oligozoospermia, and subsequent infertility [25]. It was noteworthy that infertility was not associated with any change in testosterone levels thus adding an additional advantage of using FSH based vaccine.
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Immunization of adult female sheep (ewe) with LH prohibited pregnancy in all the animals during two breeding seasons.
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Anti-hCG vaccine was the first and only birth control vaccine to go through Phase II efficacy trials successfully. The use of vaccine in sexually active women prevented them from becoming pregnant [31].
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The term gamete function is associated with the two main cells participating in gamete formation, that is, sperm and ovum. This approach targets the zona antigens of egg and surface antigens of sperm. The targets being nonhormonal provide much better safety upon other approaches. Exploiting ZP antigens as immunocontraceptive may interfere with the normal production of egg in female while sperm-based vaccine will be used in female reproductive tract to block fertilization by interfering with sperm movement or function.
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Further studies revealed that the infertility induced in immunized female rabbits was irreversible which could not be restored even after the administration of exogenous gonadotropins. Histological examination of ovaries showed the destruction of oocytes in all the growing follicles along with the depletion of resting follicles [38]. This observation indicated that the infertility was a consequence of ovarian dystrophy rather than inhibition of sperm-oocyte interaction.
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