Fertility Control in Wildlife: The Role of Immunocontraceptive Vaccines
Main Article Content
Abstract
Immunocontraception has gained significant attention as an ethical and effective tool for managing overabundant wildlife populations, particularly in regions experiencing increasing human‒wildlife conflicts due to habitat fragmentation, agricultural expansion, and urbanization. Traditional population control methods, such as culling and poisoning, have raised concerns about their environmental impact, non-target species harm and public opposition. Immunocontraceptive vaccines offer a non-lethal alternative by harnessing the body's immune response to suppress fertility, targeting key reproductive hormones and proteins, such as gonadotropin-releasing hormone (GnRH) and zona pellucida (ZP) glycoproteins. This review delves into the mechanisms of action of these vaccines, their applications across various species, and the challenges associated with immunocontraception, including inconsistent immune responses, the need for booster doses, and non-responders in treated populations. Recent advances in vaccine delivery systems, such as oral baits and slow-release implants, offer potential solutions for large-scale wildlife management efforts. Additionally, we explore the long-term ecological impacts of fertility control, its role in reducing disease transmission, and its integration into broader wildlife conservation strategies. Despite its potential, immunocontraception requires further refinement in terms of vaccine efficacy, cost-effectiveness, and practical implementation, particularly for free-ranging and hard-to-reach species. As research continues to evolve, immunocontraception holds promise for achieving sustainable wildlife population control, balancing biodiversity conservation, and mitigating human-wildlife conflicts.
Downloads
Article Details
This work is licensed under a Creative Commons Attribution 4.0 International License.
References
1. Rutberg A.T., Naugle R.E. Population-level effects of immunocontraception in white-tailed deer (Odocoileus virginianus) Wildl. Res. 2008;35:494–501.
2. White P.C.L., Ward A.I. Interdisciplinary approaches for the management of existing and emerging human–wildlife conflicts. Wildl. Res. 2010;37:623–629.
3. Gionfriddo J.P., Denicola A.J., Miller L.A., Fagerstone K.A. Efficacy of GnRH immunocontraception of wild white-tailed deer in New Jersey. Wildl. Soc. Bull. 2011;35:142–148.
4. Beringer J., Hansen L.P., Demand J.A., Sartwell J., Wallendorf M., Mange R. Efficacy of translocation to control urban deer in Missouri: costs, efficiency, and outcome. Wildl. Soc. Bull. 2002;30:767–774.
5. McCann B.E., Garcelon D.K. Eradication of feral pigs from pinnacles national monument. J. Wildl. Manag. 2008;72:1287–1295.
6. Sharp T., Saunders G. second ed. Australian Government Department of Agriculture, Fisheries and Forestry; Canberra, ACT: 2011. A Model for Assessing the Relative Humaneness of Pest Animal Control Methods. Printed by: New Millennium Print.
7. Dunn M., Marzano M., Forster J., Gill R.M.A. Public attitudes towards “pest” management: perceptions on squirrel management strategies in the UK. Biol. Conserv. 2018;222:52–63.
8. Bremner A., Park K. Public attitudes to the management of invasive non-native species in Scotland. Biol. Conserv. 2007;139:306–314.
9. Kirkpatrick J.F., Lyda R.O., Frank K.M. Contraceptive vaccines for wildlife: a review. Am. J. Reprod. Immunol. 2011;66:40–50. [PubMed] [Google Scholar]
10. Massei G., Cowan D. Fertility control to mitigate human-wildlife conflicts: a review. Wildl. Res. 2014;41:1–21. [Google Scholar]
11. Miller L.A., Rhyan J.C., Drew M. Contraception of bison by GnRH vaccine: a possible means of decreasing transmission of brucellosis in bison. J. Wildl. Dis. 2004;40:725–730. [PubMed] [Google Scholar]
12. Killian G., Fagerstone K., Kreeger T., Miller L., Rhyan J. Management strategies for addressing wildlife disease transmission: the case for fertility control. In: Nolte D.L., Arjo W.M., H S.D., editors. 12th Wildlife Damage Management Conference. 2007.
13. Ramsey D. Effects of fertility control on behavior and disease transmission in brushtail possums. J. Wildl. Manag. 2007;71:109–116. [Google Scholar]
14. Cowan PE, Tyndale-Biscoe CH. Australian and New Zealand mammal species considered to be pests or problems. Reprod Fertil Dev. 1997;9:27–36.
15. Gupta SK and Bansal P (2010) Vaccines for immunological control of fertility. Reprod Med Biol (2010) 9:61–71
16. Sridhara, Shakunthala, 2006. An Overview of Vertebrate Pests in India. Proceedings of the Vertebrate Pest Conference. UC Agriculture & Natural Resources. DOI: 10.5070/V422110078
17. Bomford M. A role for fertility control in wildlife management? Department of Primary Industries and Energy, Bureau of Rural Resources Bulletin No. 7. Australian Government Publishing Service, Canberra, Australia, 1990.
18. Drummond DC, Rennison BD. The detection of rodent resistance to antigoagulants. Bull World Health Org 1973;48:239–42.
19. Massei G., Cowan D. Fertility control to mitigate human-wildlife conflicts: a review. Wildl. Res. 2014;41:1–21. [Google Scholar
20. ]Hone J. Rate of increase and fertility control. J. Appl. Ecol. 1992;29:695–698. [Google Scholar]
21. Zhang Z. Mathematical models of wildlife management by contraception. Ecol. Model. 2000;132:105–113. [Google Scholar]
22. Merrill J.A., Cooch E.G., Curtis P.D., McCorquodale Managing an overabundant deer population by sterilization: effects of immigration, stochasticity and the capture process. J. Wildl. Manag. 2006;70:268–277. [Google Scholar]
23. Pepin K.M., Davis A.J., Cunningham F.L., VerCauteren K.C., Eckery D.C. Potential effects of incorporating fertility control into typical culling regimes in wild pig populations. PloS One. 2017;12 [PMC free article] [PubMed] [Google Scholar]
24. Yoder C.A., Miller L.A. Avian contraceptive tools: one size does not fit all. In: Timm R.M., O’Brien J.M., editors. Proc 22 Nd Vertebr Pest Conf Univ. of Calif., Davis. 2006. pp. 110–115.
25. Miller L.A., Fagerstone K.A. Induced infertility as a wildlife management tool. In: Salmon T.P., Crabb A.C., editors. Proc 19th Vertebr Pest Conf. San Diego, California. Univ. of Calif.; Davis.: 2000. pp. 160–168. [Google Scholar]
26. Curtis P.D., Pooler R.L., Richmond M.E., Miller L.A., Mattfeld G.F., Quimby F.W. Comparative effects of GnRH and porcine zona pellucida (PZP) immunocontraceptive vaccines for controlling reproduction in white-tailed deer (Odocoileus virginianus) Reprod. Suppl. 2002;60:131–141.
27. Gionfriddo J.P., Denicola A.J., Miller L.A., Fagerstone K.A. Efficacy of GnRH immunocontraception of wild white-tailed deer in New Jersey. Wildl. Soc. Bull. 2011;35:142–148.
28. Miller L.A., Fagerstone K.A., Eckery D.C. Twenty years of immunocontraceptive research: lessons learned. J. Zoo Wildl. Med. 2013;44:S84–96
29. Massei G., Koon K.K., Law S.I., Gomm M., Mora D.S.O., Callaby R. Fertility control for managing free-roaming feral cattle in Hong Kong. Vaccine. 2018;36:7393–7398
30. Miller LA, Johns BE, Killian GJ. Immunocontraception of white-tailed deer with GnRH vaccine. Am J Reprod Immunol. 2000;44:266–74.
31. Miller L.A., Gionfriddo J.P., Fagerstone K.A., Rhyan J.C., Killian G.J. The single-shot GnRH immunocontraceptive vaccine (GonaCon) in white-tailed deer: comparison of several GnRH preparations. Am. J. Reprod. Immunol. 2008;60:214–223. [PubMed] [Google Scholar]
32. Junaidi A, Williamson PE, Cummins JM, Martin GB, Blackberry MA, Trigg TE. Use of a new drug delivery formulation of the gonadotrophin-releasing hormone analogue Deslorelin for reversible long-term contraception in male dogs. Reprod Fertil Dev. 2003;15:317–22.
33. Miller LA, Johns BE, Killian GJ: Immunocontraception of white-tailed deer with GnRH vaccine. Am J Reprod Immunol 2000; 44:266–274.
34. Killian G, Fagerstone K, Kreeger T, Miller L, Rhyan J: Management strategies for addressing wildlife disease transmission: Case for fertility control. Wildl Damage Manage Conf 2008; 12:265–271.
35. Killian GJ, Miller LA, Diehl NK, Rhyan JC, Thain D: Evaluation of three contraceptive approaches for population control of wild horses. Vert Pest Conf 2004; 21:263–268.
36. Killian GJ, Diehl NK, Miller LA, Rhyan JC, Thain D: Long-term efficacy of three contraceptive approaches for population control of wild horses. Proc Vert Pest Conf 2006; 22:67–71.
37. Miller LA, Rhyan JC, Drew M: Contraception of bison by GnRH vaccine: a possible means of decreasing transmission of brucellosis in bison. J Wildl Dis 2004; 40:725–730.
38. Levy JK, Miller LA, Crawford PC, Ross MK, Fagerstone KA, Jordan HL: GnRH immunocontraception of male cats. Theriogenology 2004; 62:1116–1130.
39. Nash PB, James DK, Hui L, Miller LA: Fertility control of California ground squirrels using GnRH immunocontraception. Proc Vert Pest Conf 2004; 21:274–278.
40. Miller LA, Johns BE, Elias DJ, Crane KA: Comparative efficacy of two immunocontraceptive vaccines. Vaccine 1997; 15:1858–1862.
41. Gray ME, Thain DS, Cameron EZ and Miller LA (2010) Multi-year fertility reduction in free-roaming feral horses with single-injection immunocontraceptive formulations. Wildlife Research. 37, 475–481
42. Silin D.S., Lyubomska O.V., Jirathitikal V., Bourinbaiar A.S. Oral vaccination: where we are? Expet Opin. Drug Deliv. 2007;4:323–340.
43. Vela Ramirez J.E., Sharpe L.A., Peppas N.A. Current state and challenges in developing oral vaccines. Adv. Drug Deliv. Rev. 2017;114:116–131.
44. Antosova Z., Mackova M., Kral V., Macek T. Therapeutic application of peptides and proteins: parenteral forever? Trends Biotechnol. 2009;27:628–635.
45. Russell-Jones G.J. Oral vaccine delivery. J. Contr. Release. 2000;65:49–54
46. Bermudez L.E., Sangari F.J. Cellular and molecular mechanisms of internalization of mycobacteria by host cells. Microb. Infect. 2001;3:37–42.
47. G. Massei,∗D. Cowan,aD. Eckery,bR. Mauldin,bM. Gomm,aP. Rochaix,cF. Hill,cR. Pinkham,a and L.A. Millerb 2020. Effect of vaccination with a novel GnRH-based immunocontraceptive on immune responses and fertility in rats.Heliyon. 2020 Apr; 6(4): e03781. PMID: 32322739
48. Leenaars PPAM, Koedam MA, Wester PW, Baumans V, Claassen E, Hendriksen CFM: Assessment of side effects induced by injection of different adjuvant⁄antigen combinations in rabbits and mice. Lab Anim 1997; 32:387–406.
49. KILLIAN G, RHYAN J, DEES T, PERRY D, DOTEN H. Evaluation of gnrh contraceptive vaccine in captive feral swine in florida. (2003). USDA National Wildlife Research Center - Staff Publications . 253.
50. Lowell A. Miller**, Brad E. Johns*, Donald J. Elias? and Kenneth A. Crane* (1997)Comparative efficacy of two immunocontraceptive vaccines.Vaccine, Vol. 15, No. 17118, pp. 1858- 1862, 1997
51. A Dalmau, A Velarde, P Rodriguez, C Pedernera, P Lionch, E Fäbrega, N Casal, E Mainau, M Gispert, V King, N Slootmans, A Thomas, M Mombarg: Use of anti-GnRF vaccine to suppress estrus in cross-bred Iberian female pigs. Theriogenology 84, 342–347 (2015)
52. B Karaconji, B Lloyd, N Campbell, D Meaney, T Ahern: Effect of an antigonadotropin-releasing factor vaccine on sexual and aggressive behaviour in male pigs during the finishing period under Australian field conditions. Aust Vet J 93, 121–123 (2015)
53. I Lueders, TB Hildebrandt, C Gray, S Botha, P Rich, C Niemuller: Supression of testicular function in a male Asian elephant (Elephas maximus) treated with gonadotropin-releasing hormone vaccines. J Zoo Wildl Med 45, 611–619 (2014)
54. F Janet, T Gerig, AC Tschuor, S Amatayakul-Chantler, J Walker, R Howard, H Bollwein, R Thun: Vaccination against gonadotropin-releasing factor (GnRF) with Bopriva significantly decreases testicular development, serum testosterone levels and physical activity in pubertal bulls. Theriogenology 78, 182–188 (2012) DOI: 10.1016/j.theriogenology.2012.01.035
55. G Theubet, R Thun, M Hilbe, F Janett: Effect of vaccination against GnRH (Bopriva®) in the male pubertal calf. Schweiz Arch Tierheilkd 152, 459–469 (2010) DOI: 10.1024/0036-7281/a000106
56. N Wicks, S Crouch, CA Pearl: Effects of Improvac and Bopriva on the testicular function of boars ten weeks after immunization. Anim Reprod Sci 142, 149– 159 (2013) DOI: 10.1016/j.anireprosci.2013.09.017
57. L Balet, F Janett, J Hüsler, M Piechotta, R Howard, S Amatayakul-Chantler, A Steiner, G Hirsbrunner: Immunization against gonadotropin-releasing hormone in dairy cattle: antibody titres, ovarian function, hormonal levels, and reversibility. J Dairy Sci 97, 2193–2203 (2014) DOI: 10.3168/jds.2013-7602
58. SM Skinner, T Mills, HJ Kirchick, BS Dunbar: Immunisation with zona pellucida proteins results in abnormal ovarian follicular differentiation and inhibition of gonadotropininduced steroid secretion. Endocrinology 115, 2418–2432 (1984) DOI: 10.1210/endo-115-6-2418
59. CA Mahi-Brown, R Yanagimachi, JC Hoffman, TT Huang Jr: Fertility control in the bitch by active immuniation with porcine zonae pellucidae: use of different adjuvants and patterns of estradiol and progesterone levels in estrous cycles. Biol Reprod 32, 761–772 (1985)
60. AG Sacco, DL Pierce, MG Subramanian, EC Yurewicz, WR Dukelow: Ovaries remain functional in squirrel monkeys (Saimiri sciureus) immunized with porcine zona pellucida 55,000 macromolecule. Biol Reprod 36, 481–490 (1987) DOI: 10.1095/biolreprod36.2.481
61. H Bagavant, P Thillai-Koothan, MG Sharma, GP Talwar, SK Gupta: Antifertility effects of porcine zona pellucida-3 immunization using permissible adjuvants in female bonnet monkeys (Macaca radiata): reversibility, effect on follicular development and hormonal profiles. J Reprod Fertil 102, 17–25 (1994) DOI: 10.1530/jrf.0.1020017
62. IKM Liu, M Bernoco, M Feldman: Contraception in mares heteroimmunized with pig zonae pellucidae. J. Reprod Fertil 85, 19–29 (1989) DOI: 10.1530/jrf.0.0850019
63. LA Miller, BE Johns, GJ Killian: Long-term effects of PZP immunization on reproduction in white-tailed deer. Vaccine 18, 568–574 (2000) DOI: 10.1016/S0264-410X(99)00165-6
64. JF Kirkpatrick, JW Turner Jr, IKM Liu, R Fayrer-Hosken: Application of pig zona pellucida immunocontraception to wildlife fertility control. J Reprod Fertil Suppl 50, 183–189 (1996
65. RA Fayrer-Hosken, D Grobler, JJ van Altena, HJ Bertschinger, JF Kirkpatrick: Immunocontraception of African elephants. Nature 407, 149 (2000) DOI: 10.1038/35025136
66. JF Kirkpatrick, A Turner: Achieving population goals in a long-lived wildlife species (Equus caballus) with contraception. Wildl Res 35, 513–519 (2008) DOI: 10.1071/WR07106
67. JF Kirkpatrick, AT Rutberg, L CoatesMarkle: Immunocontraceptive Reproductive Control Utilizing Porcine ZonaPellucida (PZP) in Federal Wild Horse Populations (fourth edition), 1–41 (2012). http://www. sccpzp.org/wp-content/uploads/PZPQAJune-6–2012.pdf
68. PD Curtis, RL Pooler, ME Richmond, LA Miller, GF Mattfeld, FW Quimby: Comparative effects of GnRH and porcine zona pellucida (PZP) immunocontraceptive vaccines for controlling reproduction in white-tailed deer (Odocoileus virginianus). Reprod Suppl 60, 131–141 (2002)
69. SE Shideler, MA Stoops, NA Gee, JA Howell: Use of porcine zona pellucida (PZP) vaccine as a contraceptive agent in free-ranging elk (Cervus elaphus nannodes). Reproduction Suppl 60, 169–176 (2002)
70. A Delink, JJ van Altena, D Grobler, H Bertschinger, JF Kirkpatrick, R Slotow: Implementing immunocontraception in free-ranging African elephants at Makalali Conservancy. J S Afr Vet Assoc 78, 25–30 (2007
71. AT Rutberg, RE Naugle, F Verret: Single-treatment porcine zona pellucida immunocontraception associated with reduction of a population of white-tailed deer (Odocoileus virginianus). J Zoo Wildl Med 44, S75–83 (2013)
72. . JW Turner, IKM Liu, DR Flanagan, AT Rutberg, JF Kirkpatrick: Immunocontraception in wild horses: one inoculation provides two years of infertility. J Wildl Manage 71, 662–667 (2007)
73. VS Palm, AG Sacco, FN Synder, MG Subramanian: Tissue specificity of porcine zona pellucida antigen(s) tested by radioimmunoassay. Biol Reprod 21, 709– 713 (1979) DOI: 10.1095/biolreprod21.3.709
74. MR Barber, RA Fayrer-Hosken: Evaluation of somatic and reproductive immunotoxic effects of the porcine zona pellucida vaccination. J Exp Zool 286, 641–646 (2000).
75. SM Skinner, T Mills, HJ Kirchick, BS Dunbar: Immunisation with zona pellucida proteins results in abnormal ovarian follicular differentiation and inhibition of gonadotropininduced steroid secretion. Endocrinology 115, 2418–2432 (1984) DOI: 10.1210/endo-115-6-2418
76. CA Mahi-Brown, R Yanagimachi, JC Hoffman, TT Huang Jr: Fertility control in the bitch by active immuniation with porcine zonae pellucidae: use of different adjuvants and patterns of estradiol and progesterone levels in estrous cycles. Biol Reprod 32, 761–772 (1985).
77. JF Kirkpatrick, IKM Liu, JW Turner: Remotely delivered immunocontraception n feral hoses. Wildl Soc Bull 18, 326–330 (1990).
78. RE Naugle, AT Rurberg, HB Underwood, JW Turner Jr., IK Liu: Field testing of immunocontraception on white-tailed deer (Odocoileus virginianus) on Fire Island National Seashore, New York, USA. Reprod Suppl 60, 143–153 (2002).
79. HS Mason, TA Haq, JD Clements, CJ Arntzen: Edible vaccine protects mice against Escherichia coli heat-labile enterotoxin (LT): potatoes expressing a synthetic LT-B gene. Vaccine 15, 1336– 1343 (1998) DOI: 10.1016/S0264-410X(98)80020-0
80. CO Tacket, HS Mason, G Losonsky, JD Clements, MM Levine, CJ Arntzen: Immunogenicity in humans of a recombinant bacterial antigen delivered in potatoes. Nature Medicine 4, 607–609 (1998) DOI: 10.1038/nm0598-607
81. I Polkinghorne, D Hamerli, P Cowen, J Duckworth: Plant-based immunocontraceptive control of wildlife – “potentials, limitations, and possums”. Vaccine 23, 1847–1850 (2005) DOI: 10.1016/j.vaccine.2004.11.016
82. EVL Grgacic, DA Anderson: Virus-like particles: passport to immune recognition. Methods 40, 60–65 (2006) DOI: 10.1016/j.ymeth.2006.07.018.
83. S Choudhury, V Kakkar, P Suman, K Chakrabarti, S Vrati, SK Gupta: Immunogenicity of zona pellucida glycoprotein-3 and spermatozoa YLP(12) peptides presented on Johnson grass mosaic virus-like p articles. Vaccine 27, 2948–2953 (2009)
84. P Walcher, X Cui, JA Arrow, S Scobie, FC Molinia, PE Cowan, W Lubitz, JA Duckworth: Bacterial ghosts as a delivery system for zona pellucida-2 fertility control vaccines for brushtail possums (Trichosurus vulpecula). Vaccine 26, 6832–6838 (2008).
85. X Zhang, YH Lou, M Koopman, T Doggett, KS Tung, R Curtiss 3rd: Antibody responses and infertility in mice following oral immunization with attenuated Salmonella typhimurium expressing recombinant murine ZP3. Biol Reprod 56, 33–41 (1997).
86. RJ Jackson, DJ Maguire, LA Hinds, IA Ramshaw: Infertility in mice induced by a recombinant ectromelia virus expressing mouse zona pellucida glycoprotein 3. Biol Reprod 58, 152–159 (1998) DOI: 10.1095/biolreprod58.1.152
87. W Gu, M Holland, P Janssens, R Seamark, P Kerr: Immune response in rabbit ovaries following infection of a recombinant myxoma virus expressing rabbit zona pellucida protein B. Virology 318, 516–523 (2004) DOI: 10.1016/j.virol.2003.10.021
88. . SM Mackenzie, EA McLaughlin, HD Perkins, N French, T Sutherland, RJ Jackson, B Inglis, WJ Müller, BH van Leeuwen, AJ Robinson, PJ Kerr: Immunocontraceptive effects on female rabbits infected with recombinant myxoma virus expressing rabbit ZP2 or ZP3. Biol Reprod 74, 511–521 (2006)
89. CM Hardy, LA Hinds, PJ Kerr, ML Lloyd, AJ Redwood, GR Shellam, T Strive: Biological control of vertebrate pests using virally vectored immunocontraception. J Reprod Immunol 71, 102–111 (2006) DOI: 10.1016/j.jri.2006.04.006
90. RG Brown, WD Bowen, JD Eddington, WC Kimmins, M Mezei, JL Parsons, B Pohajdak: Evidence for a long-lasting single administration contraceptive vaccine in wild grey seals. J Reprod Immunol 35, 43–51 (1997).
91. V Kanchan, AK Panda: Interactions of antigen-loaded polylactide particles with macrophages and their correlation with the immune response. Biomaterials 28, 5344– 5357 (2007) DOI: 10.1016/j.biomaterials.2007.08.015
92. V Kanchan, YK Katare, AK Panda: Memory antibody response from antigen loaded polymer particles and the effect of antigen release kinetics. Biomaterials 30, 4763– 4776 (2009)
93. Edwards RG. Immunological control of fertility in female mice. Nature 1964; 203:50 - 3; http://dx.doi.org/10.1038/203050a0; PMID: 14197348
94. Thau RB, Sundaram K, Thornton YS, Seidman LS. Effects of immunization with the β-subunit of ovine luteinizing hormone on corpus luteum function in the rhesus monkey. Fertil Steril 1979; 31:200 - 4; PMID: 104890.
95. Remy JJ, Bozon V, Couture L, Goxe B, Salesse R, Garnier J. . Suppression of fertility in male mice by immunization against LH receptor. J Reprod Immunol 1993; 25:63 - 79; http://dx.doi.org/10.1016/0165-0378(93)90042-G; PMID: 8271240
96. Roberts AJ, Reeves JJ. Reproductive and endocrine changes in ewes actively immunized against luteinizing hormone. Journal of Reproductive Immunology. 1989;16(2):187–197.
97. Murty GSRC, Rani CSS, Moudgal NR, Prasad MRN. Effect of passive immunization with specific antiserum to FSH on the spermatogenic process and fertility of adult male bonnet monkeys (Macaca radiata) Journal of Reproduction and Fertility. 1979;26:147–163.