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Evaluation of immunocontraceptive vaccine composed of gonadotropin-releasing hormone conjugated with granulocyte-macrophage colony-stimulating factor in male rats

  • Park, Byung-Joo (Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University) ;
  • Kim, Yong-Hyun (Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University) ;
  • Ahn, Hee-Seop (Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University) ;
  • Han, Sang-Hoon (Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University) ;
  • Go, Hyeon-Jeong (Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University) ;
  • Lee, Joong-Bok (Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University) ;
  • Park, Seung-Yong (Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University) ;
  • Song, Chang-Seon (Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University) ;
  • Lee, Sang-Won (Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University) ;
  • Choi, In-Soo (Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University)
  • Received : 2017.06.21
  • Accepted : 2017.07.25
  • Published : 2017.09.30

Abstract

Surgical castration performed to reduce male-associated problems results in pain and microbial infections in male animals. Therefore, immunocontraception, which is mediated by the animal's own antibodies against reproductive hormones, has been recommended as an alternative to surgical castration when considering the animal's welfare. In this study, a new immunocontraceptive vaccine composed of six tandem copies of gonadotropin-releasing hormone (GnRH) fused to rat granulocyte-macrophage colony-stimulating factor (GM-CSF) was developed, and its efficacy was evaluated in male rats. Three different doses (10, 50, and $100{\mu}g$) of recombinant GM-CSF-GnRH protein were injected three times at intervals of two weeks into male rats. The rats vaccinated with three doses of GM-CSF-GnRH produced a significantly higher level of antibodies against GnRH than that in the negative control rats. Severe atrophy of gonads was observed in rats vaccinated with three doses of GM-CSF-GnRH but not in the negative control rats. The results reveal that the new GnRH vaccine conjugated with rat GM-CSF induces efficient immunocontraception in male rats. This formulation of the immunocontraceptive vaccine would be applicable to both domestic and pet male animals.

Acknowledgement

Supported by : Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries (IPET)

References

  1. Adams TE, Daley CA, Adams BM, Sakurai H. Testes function and feedlot performance of bulls actively immunized against gonadotropin-releasing hormone: effect of age at immunization. J Anim Sci 1996, 74, 950-954. https://doi.org/10.2527/1996.745950x
  2. Bonneau M, Enright WJ. Immunocastration in cattle and pigs. Livest Prod Sci 1995, 42, 193-200. https://doi.org/10.1016/0301-6226(95)00020-L
  3. Casares S, Inaba K, Brumeanu TD, Steinman RM, Bona CA. Antigen presentation by dendritic cells after immunization with DNA encoding a major histocompatibility complex class II–restricted viral epitope. J Exp Med 1997, 186, 1481-1486. https://doi.org/10.1084/jem.186.9.1481
  4. Chattergoon MA, Robinson TM, Boyer JD, Weiner DB. Specific immune induction following DNA-based immunization through in vivo transfection and activation of macrophages/ antigen-presenting cells. J Immunol 1998, 160, 5707-5718.
  5. Condon C, Watkins SC, Celluzzi CM, Thompson K, Falo LD Jr. DNA-based immunization by in vivo transfection of dendritic cells. Nat Med 1996, 2, 1122-1128. https://doi.org/10.1038/nm1096-1122
  6. Dela Cruz JS, Trinh KR, Morrison SL, Penichet ML. Recombinant anti-human HER2/neu IgG3-(GM-CSF) fusion protein retains antigen specificity and cytokine function and demonstrates antitumor activity. J Immunol 2000, 165, 5112-5121. https://doi.org/10.4049/jimmunol.165.9.5112
  7. Dranoff G, Jaffee E, Lazenby A, Golumbek P, Levitsky H, Brose K, Jackson V, Hamada H, Pardoll D, Mulligan RC. Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci U S A 1993, 90, 3539-3543. https://doi.org/10.1073/pnas.90.8.3539
  8. Dunshea FR, Colantoni C, Howard K, McCauley I, Jackson P, Long KA, Lopaticki S, Nugent EA, Simons JA, Walker J, Hennessy DP. Vaccination of boars with a GnRH vaccine (Improvac) eliminates boar taint and increases growth performance. J Anim Sci 2001, 79, 2524-2535. https://doi.org/10.2527/2001.79102524x
  9. Ferro VA, Khan MAH, McAdam D, Colston A, Aughey E, Mullen AB, Waterston MM, Harvey MJA. Efficacy of an anti-fertility vaccine based on mammalian gonadotrophin releasing hormone (GnRH-I)-a histological comparison in male animals. Vet Immunol Immunopathol 2004, 101, 73-86. https://doi.org/10.1016/j.vetimm.2004.03.011
  10. Goubau S, Silversides DW, Gonzalez A, Laarveld B, Mapletoft R, Murphy BD. Immunization of sheep against modified peptides of gonadotropin releasing hormone conjugated to carriers. Domest Anim Endocrinol 1989, 6, 339-347. https://doi.org/10.1016/0739-7240(89)90028-3
  11. Jung MJ, Moon YC, Cho IH, Yeh JY, Kim SE, Chang WS, Park SY, Song CS, Kim HY, Park KK, McOrist S, Choi IS, Lee JB. Induction of castration by immunization of male dogs with recombinant gonadotropin-releasing hormone (GnRH)-canine distemper virus (CDV) T helper cell epitope p35. J Vet Sci 2005, 6, 21-24.
  12. Kass E, Parker J, Schlom J, Greiner JW. Comparative studies of the effects of recombinant GM-CSF and GM-CSF administered via a poxvirus to enhance the concentration of antigen-presenting cells in regional lymph nodes. Cytokine 2000, 12, 960-971. https://doi.org/10.1006/cyto.2000.0684
  13. Mach N, Dranoff G. Cytokine-secreting tumor cell vaccines. Curr Opin Immunol 2000, 12, 571-575. https://doi.org/10.1016/S0952-7915(00)00144-8
  14. Maecker HT, Umetsu DT, DeKruyff RH, Levy S. Cytotoxic T cell responses to DNA vaccination: dependence on antigen presentation via class II MHC. J Immunol 1998, 161, 6532-6536.
  15. Metcalf D. The granulocyte-macrophage colony-stimulating factors. Science 1985, 229, 16-22. https://doi.org/10.1126/science.2990035
  16. Operschall E, Schuh T, Heinzerling L, Pavlovic J, Moelling K. Enhanced protection against viral infection by coadministration of plasmid DNA coding for viral antigen and cytokines in mice. J Clin Virol 1999, 13, 17-27. https://doi.org/10.1016/S1386-6532(99)00008-6
  17. Porgador A, Irvine KR, Iwasaki A, Barber BH, Restifo NP, Germain RN. Predominant role for directly transfected dendritic cells in antigen presentation to $CD8^+$ T cells after gene gun immunization. J Exp Med 1998, 188, 1075-1082. https://doi.org/10.1084/jem.188.6.1075
  18. Sin JI, Sung JH, Suh YS, Lee AH, Chung JH, Sung YC. Protective immunity against heterologous challenge with encephalomyocarditis virus by VP1 DNA vaccination: effect of coinjection with a granulocyte-macrophage colony stimulating factor gene. Vaccine 1997, 15, 1827-1833. https://doi.org/10.1016/S0264-410X(97)88856-1
  19. Syrengelas AD, Chen TT, Levy R. DNA immunization induces protective immunity against B-cell lymphoma. Nat Med 1996, 2, 1038-1041. https://doi.org/10.1038/nm0996-1038
  20. Tarr PE. Granulocyte-macrophage colony-stimulating factor and the immune system. Med Oncol 1996, 13, 133-140. https://doi.org/10.1007/BF02990841
  21. Thompson DL Jr. Immunization against GnRH in male species (comparative aspects). Anim Reprod Sci 2000, 60-61, 459-469. https://doi.org/10.1016/S0378-4320(00)00116-0
  22. Ulker H, Y lmaz A, Karakup F, Yoruk M, Budag C, DeAvila DM, Reeves JJ. LHRH fusion protein immunization alters testicular development, ultrasonographic and histological appearance of ram testis. Reprod Domest Anim 2009, 44, 593-599. https://doi.org/10.1111/j.1439-0531.2007.01024.x