Milestones in contraceptive vaccines development and hurdles in their application

Figures & data

Table 1. Contraceptive vaccines for wildlife population management and their relevance for human contraception

Target species	Vaccine formulations	Observations	Relevance for human contraceptive vaccine
Male pigs	GnRH-based contraceptive vaccines; Improvac^R	Immunization of male pigs led to immuno-castration and improvement in the meat quality.	Observed inhibition of gonadotropins, sex steroid hormones, atrophy of testes and prostate, contraindicate its use in humans
Wild horses (Equus caballus)	Native porcine ZP proteins	Used to manage the population of wild horses at Assateague Island National Seashore, MD, USA.	Safety of long-term vaccination encourage exploration of ZP-based contraceptive vaccine for humans
White-tailed deer (Odocoileus virginianus)	GnRH-based contraceptive vaccines; GonaCon^TM Native porcine ZP proteins	Active immunization led to reduction in their fawning rates Used to manage the population of white-tailed deer inhabiting Fire Island National Seashore, NY, USA.	GnRH-based contraceptive vaccine are not proposed for humans due to disturbed hormonal profile For humans, ZP-based immunogens should be devoid of oophoritogenic epitopes
African elephant (Loxodonta africana)	Native porcine ZP proteins	Inhibition of fertility in the immunized female elephants.	Heterologous immunization feasible

Table 2. Clinical trials of contraceptive vaccines in humans

Immunogen	Salient findings	References
oFSH	Immunization of men with oFSH led to generation of bio-neutralizing antibodies. Reduction in sperm count observed in some immunized subjects. No change in LH, testosterone and TSH concentration.	48
CTP of β-hCG (aa residues 109–145) conjugated to DT	Immunization of 30 sterilized women revealed vaccine to be immunogenic and safe.	141
β-hCG-TT	Immunization studies in women revealed vaccine to be immunogenic and safe. Antibodies thus generated neutralized hCG. Women with low antibody titers were not protected from pregnancy.	143, 144, 145, 146
β-hCG-α-oLH-TT/ β-hCG-α-oLH- DT	Phase II clinical trials in fertile women revealed it to be safe and more immunogenic as compared with β-hCG-TT. Only one pregnancy reported from 1224 mating cycles in women having anti-hCG antibody titers above 50 ng/ml. Inhibition of fertility was reversible.	147, 148

Table 3. Strength and weakness of various contraceptive vaccines

Target	Strength	Weakness	Clinical application
GnRH	Workable in both males and females. Contraceptive efficacy demonstrated in animals	Inhibit secretion of gonadotropins, sex steroid hormones and atrophy of reproductive organs	Useful for veterinary application. Not likely to be used in humans
LH	Contraceptive efficacy evaluated in non-human primates	Disturbance in steroid hormonal profile	Not being pursued for veterinary or human use
FSH	Extensive immunization studies in non-human primates. Phase I clinical studies in men	Discrepant results on the efficacy to decrease spermatogenesis in non-human primates	Additional safety and efficacy studies needed
Sperm-specific proteins	Several sperm-specific proteins documented and contraceptive efficacy established in animals	Long-term safety studies not performed	Good candidate for development of contraceptive vaccine for humans
Zona pellucida	Contraceptive efficacy demonstrated in animals. Long-term follow-up of immunized animals showed no debilitating effect on health	Generate oophoritis	Useful for veterinary application. Immunogen design not eliciting oophoritis critical for human use
hCG	Safety studies performed. Demonstrated contraceptive efficacy in women. Block in fertility reversible	Inadequate protective antibody titers in all vaccinated women. Variability in immune response among women	Good candidate for developing contraceptive vaccine for humans

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