Skip to main content

Advertisement

Log in

Granulocyte—Macrophage Colony-Stimulating Factor Enhances the Humoral Immune Responses of Mouse Zona Pellucida 3 Vaccine Strategy Based on DNA and Protein Coadministration in BALB/c Mice

  • Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

We recently demonstrated that co-administration of mouse zona pellucida 3 (mZP3) DNA and protein vaccine enhanced the contraception of mice by increasing humoral immune responses. In this study, we try to use granulocyte—macrophage colony-stimulating factor (GM-CSF) to further improve the humoral immune responses induced by mZP3 DNA and protein co-administration. BALB/c mice were intranasally pre-injected with GM-CSF 4 days before co-administration. Compared to DNA and protein coadministration without GM-CSF, the combination of GM-CSF and coadministration significantly enhances humoral immune responses, especially the level of secretory immunoglobulin A (sIgA) in vaginal washes. The enhanced antibody responses are correlated with the upregulated level of interleukin 4 (IL-4) and enhanced maturation of dendritic cells (DCs). Thus, GM-CSF is a potential candidate adjuvant to be used for the development of a safe and effective contraceptive vaccine.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Aitken RJ, Paterson M, van Duin M. The potential of the zona pellucida as a target for immunocontraception. Am J Reprod Immunol. 1996;35(3):175–180.

    Article  CAS  Google Scholar 

  2. Greenhouse S, Castle PE, Dean J. Antibodies to human ZP3 induce reversible contraception in transgenic mice with ‘humanized’ zonae pellucidae. Hum Reprod. 1999;14(3):593–600.

    Article  CAS  Google Scholar 

  3. Bleil JD, Wassarman PM. Structure and function of the zona pellucida: identification and characterization of the proteins of the mouse oocyte’s zona pellucida. Dev Biol. 1980;76(1):185–202.

    Article  CAS  Google Scholar 

  4. Shimizu S, Tsuji M, Dean J. In vitro biosynthesis of three sulfated glycoproteins of murine zonae pellucidae by oocytes grown in follicle culture. J Biol Chem. 1983;258(9):5858–5863.

    CAS  PubMed  Google Scholar 

  5. Paterson M, Koothan PT, Morris KD, et al. Analysis of the contraceptive potential of antibodies against native and deglycosylated porcine ZP3 in vivo and in vitro. Biol Reprod. 1992;46(4): 523–534.

    Article  CAS  Google Scholar 

  6. Paterson M, Wilson MR, Morris KD, van Duin M, Aitken RJ. Evaluation of the contraceptive potential of recombinant human ZP3 and human ZP3 peptides in a primate model: their safety and efficacy. Am J Reprod Immunol. 1998;40(3):198–209.

    Article  CAS  Google Scholar 

  7. Clydesdale G, Pekin J, Beaton S, Jackson RJ, Vignarajan S, Hardy CM. Contraception in mice immunized with recombinant zona pellucida subunit 3 proteins correlates with Th2 responses and the levels of interleukin 4 expressed by CD4+ cells. Reproduction. 2004;128(6):737–745.

    Article  CAS  Google Scholar 

  8. Jackson RJ, Maguire DJ, Hinds LA, Ramshaw IA. Infertility in mice induced by a recombinant ectromelia virus expressing mouse zona pellucida glycoprotein 3. Biol Reprod. 1998;58(1): 152–159.

    Article  CAS  Google Scholar 

  9. Lloyd ML, Shellam GR, Papadimitriou JM, Lawson MA. Immunocontraception is induced in BALB/c mice inoculated with murine cytomegalovirus expressing mouse zona pellucida 3. Biol Reprod. 2003;68(6):2024–2032.

    Article  CAS  Google Scholar 

  10. Hasegawa A, Hamada Y, Shigeta M, Koyama K. Contraceptive potential of synthetic peptides of zona pellucida protein (ZPA). J Reprod Immunol. 2002;53(1–2):91–98.

    Article  CAS  Google Scholar 

  11. Sivapurapu N, Upadhyay A, Hasegawa A, Koyama K, Gupta SK. Native zona pellucida reactivity and in-vitro effect on human sperm-egg binding with antisera against bonnet monkey ZP1 and ZP3 synthetic peptides. J Reprod Immunol. 2002;56(1–2):77–91.

    Article  CAS  Google Scholar 

  12. Ringleb J, Rohleder M, Jewgenow K. Impact of feline zona pellucida glycoprotein B-derived synthetic peptides on in vitro fertilization of cat oocytes. Reproduction. 2004;127(2):179–186.

    Article  CAS  Google Scholar 

  13. Borillo J, Coonrod SA, Wu J, Zhou C, Lou Y. Antibodies to two ZP3 B cell epitopes affect zona pellucida assembly. J Reprod Immunol. 2008;78(2):149–157.

    Article  CAS  Google Scholar 

  14. Hardy CM, Beaton S, Hinds LA. Immunocontraception in mice using repeated, multi-antigen peptides: immunization with purified recombinant antigens. Mol Reprod Dev. 2008;75(1):126–135.

    Article  Google Scholar 

  15. Li J, Jin H, Zhang A, Li Y, Wang B, Zhang F. Enhanced contraceptive response by co-immunization of DNA and protein vaccines encoding the mouse zona pellucida 3 with minimal oophoritis in mouse ovary. J Gene Med. 2007;9(12):1095–1103.

    Article  CAS  Google Scholar 

  16. Zhang A, Li J, Zhao G, et al. Intranasal co-administration with the mouse zona pellucida 3 expressing construct and its coding protein induces contraception in mice. Vaccine. 2011;29(39): 6785–6792.

    Article  CAS  Google Scholar 

  17. Perales MA, Yuan J, Powel S, et al. Phase I/II study of GM-CSF DNA as an adjuvant for a multipeptide cancer vaccine in patients with advanced melanoma. Mol Ther. 2008;16(12):2022–2029.

    Article  CAS  Google Scholar 

  18. Qing Y, Chen M, Zhao J, et al. Construction of an HBV DNA vaccine by fusion of the GM-CSF gene to the HBV-S gene and examination of its immune effects in normal and HBV-transgenic mice. Vaccine. 2010;28(26):4301–4307.

    Article  CAS  Google Scholar 

  19. Hirata Y, Egea L, Dann SM, Eckmann L, Kagnoff MF. GM-CSF-facilitated dendritic cell recruitment and survival govern the intestinal mucosal response to a mouse enteric bacterial pathogen. Cell Host Microbe. 2010;7(2):151–163.

    Article  CAS  Google Scholar 

  20. Jones T, Stern A, Lin R. Potential role of granulocyte-macrophage colony-stimulating factor as vaccine adjuvant. Eur J Clin Microbiol Infect Dis. 1994;13 (suppl 2):S47–S53.

    Article  Google Scholar 

  21. Inaba K, Inaba M, Romani N, et al Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. J Exp Med. 1992;176(6):1693–1702.

    Article  CAS  Google Scholar 

  22. Kusakabe K, Xin KQ, Katoh H, et al. The timing of GM-CSF expression plasmid administration influences the Th1/Th2 response induced by an HIV-1-specific DNA vaccine. J Immunol. 2000;164(6):3102–3111.

    Article  CAS  Google Scholar 

  23. Illum L, Jabbal-Gill I, Hinchcliffe M, Fisher AN, Davis SS. Chitosan as a novel nasal delivery system for vaccines. Adv Drug Deliv Rev. 2001;51(1–3):81–96.

    Article  CAS  Google Scholar 

  24. Nishi E, Kume N, Ueno Y, Ochi H, Moriwaki H, Kita T. Lysophosphatidylcholine enhances cytokine-induced interferon gamma expression in human T lymphocytes. Circ Res. 1998;83(5): 508–515.

    Article  CAS  Google Scholar 

  25. Perrin-Cocon L, Agaugue S, Coutant F, et al. Lysophosphatidylcholine is a natural adjuvant that initiates cellular immune responses. Vaccine. 2006;24(9):1254–1263.

    Article  CAS  Google Scholar 

  26. Sung CM, Yeh CT, Shiau SS, Liang CK, Chang ML. Hydrodynamics-based transfection of the combination of betacellulin and neurogenic differentiation 1 DNA ameliorates hyperglycemia in mice with streptozotocin-induced diabetes. Diabetes Technol Ther. 2011;13:519–525.

    Article  CAS  Google Scholar 

  27. Hardy CM, ten Have JF, Mobbs KJ, Hinds LA. Assessment of the immunocontraceptive effect of a zona pellucida 3 peptide antigen in wild mice. Reprod Fertil Dev. 2002;14(3–4):151–155.

    Article  CAS  Google Scholar 

  28. Mellstedt H, Fagerberg J, Osterborg A. Local low-dose of soluble GM-CSF significantly augments an immune response against tumour antigens in man. Eur J Cancer. 1999;35 (suppl 3): S29–S32.

    Article  CAS  Google Scholar 

  29. Hardy CM, ten Have JF, Pekin J, Beaton S, Jackson RJ, Clydesdale G. Contraceptive responses of mice immunized with purified recombinant mouse zona pellucida subunit 3 (mZP3) proteins. Reproduction. 2003;126(1):49–59.

    Article  CAS  Google Scholar 

  30. Naz RK, Chauhan SC. Human sperm-specific peptide vaccine that causes long-term reversible contraception. Biol Reprod. 2002;67(2):674–680.

    Article  CAS  Google Scholar 

  31. Lou YH, Park KK, Agersborg S, Alard P, Tung KS. Retargeting T cell-mediated inflammation: a new perspective on autoantibody action. J Immunol. 2000;164(10):5251–5257.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Jinyao Li PhD or Fuchun Zhang PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kadir, Z., Ma, X., Li, J. et al. Granulocyte—Macrophage Colony-Stimulating Factor Enhances the Humoral Immune Responses of Mouse Zona Pellucida 3 Vaccine Strategy Based on DNA and Protein Coadministration in BALB/c Mice. Reprod. Sci. 20, 400–407 (2013). https://doi.org/10.1177/1933719112459236

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719112459236

Keywords

Navigation