Development of male contraceptive vaccine - a perspective

Abstract

This paper reviews the recent advances that have occurred in the area of development of a male contraceptive vaccine. The vaccine candidates considered for review are hormone/hormone receptor-based proteins including luteinizing hormone-releasing hormone (LHRH)/LH, follicle stimulating hormone (FSH), as well as LH and FSH receptor proteins. The review also highlights the advances in our basic understanding of gonadotrophin action which have led to development of these vaccines. Focus is mainly on studies in the non-human primate which may be directly relevant to projected studies in the human. The data indicate that the vaccines are well tolerated by the primate (including the human based on limited data) and do not give rise to any known toxic symptoms or immediate health hazards. The response to the immunogen has been uniform and it may be possible to increase antibody titres as well as prolong the immune response by adding acceptable immune stimulators to the adjuvant cocktail and developing better immunization schedules or immunogen delivery systems. Contraceptive vaccines for the male are a feasible proposition and attention should now be focussed on evaluating carefully the bioefficacy of antibodies raised to recombinant ovine FSHbeta or FSH receptor protein fragments in both human and non-human primates. The advantage of the FSH/FSH receptor over the LHRH/LH-based vaccine lies in the fact that the former does not require an exogenous testosterone supplement to maintain accessory gland function, libido etc. The LHRH/LH-based vaccine results in azoospermia, while the FSH vaccine causes the production of low numbers of poor quality spermatozoa which are incapable of impregnating cycling females.

Milestones in contraceptive vaccines development and hurdles in their application

“…The block in fertility was reversible as concomitant with the decline in the anti-oFSH antibody levels, animals regained fertility. 47 Active immunization with oFSH did not lead to any side effects. 47 Keeping in view the encouraging observations in nonhuman primates, the group headed by Prof N. R. Moudgal, Indian Institute of Science, Bangalore, India undertook a pilot study in humans, wherein 5 men were immunized with oFSH ( Table 2).…”

Update on Male Hormonal Contraception: Is the Vasectomy in Jeopardy?

“…94 Several attempts have been made to couple mammalian GnRH, a nonimmunogenic peptide, to carrier proteins such as tetanus and diphtheria toxoids to enhance the bioefficacy of the antibodies produced. 95 Anti-GnRH vaccines have been tested for control of prostate cancers in India, in hopes of cutting off androgen support to prostate cancer cells. 96 Although there have been reports of contraceptive efficacy in male dogs, there have been no successful structured studies in male nonhuman primates that have carefully evaluated such a contraceptive vaccine.…”

“…96 Although there have been reports of contraceptive efficacy in male dogs, there have been no successful structured studies in male nonhuman primates that have carefully evaluated such a contraceptive vaccine. 95 Other possible vaccine targets include gonadotropins and gonadotropin receptors. Human FSH and ovine FSH are the two such candidate antigens.…”

“…The fertility of male monkeys after hFSH immunization was significantly reduced, as described as loss in spermatozoa ability to penetrating hamster ova assay. 95 Even though FSH-based vaccines may not lead to azoospermia, there seems to be increasing evidence that a reduction in the quality of sperm combined with oligospermia may represent a reasonable marker for male contraception as a measure of infertility. Furthermore, using FSH protein fragments instead of GnRH-or LH-based vaccines does not require exogenous testosterone supplementation to maintain accessory gland function and libido.…”

“…Furthermore, using FSH protein fragments instead of GnRH-or LH-based vaccines does not require exogenous testosterone supplementation to maintain accessory gland function and libido. 95 Periodic vaccination as a method for male contraception represents a promising area of research and continues to be refined through the use of better adjuvant compounds.…”