Immunisation with a plasmid DNA vaccine encoding gonadotrophin releasing hormone (GnRH-I) and T-helper epitopes in saline suppresses rodent fertility

Vaccine. 2008 Mar 4;26(10):1365-74. doi: 10.1016/j.vaccine.2007.12.052. Epub 2008 Jan 22.

Abstract

Research into active immunisation against gonadotrophin releasing hormone (GnRH-I) has gained widespread acceptance as a means of controlling reproduction and behaviour of farm, companion and wild animals. Many studies describe the use of multiple copies of the self-peptide in linear alignment and conjugation with a large carrier protein to increase the immune response to the peptide. However, problems resulting from carrier protein epitope suppression have seen a diversion of interest into the use of genetic materials to elicit an optimum immune response. In this study, a 533-bp long DNA vaccine was constructed in pcDNAV5-HisB coding for 18.871 kDa GnRH-I-T-helper-V5 epitopes fusion protein. COS1 cells transfected with the vaccine construct were found to release fusion protein into culture supernatant. The vaccine construct (100 microg/mice) in saline solution administered into the anterior quadriceps muscle of ICR male and female mice stimulated antigen-specific IgG antibody responses. Testosterone levels in the vaccinated male mice were significantly (p = 0.021) reduced. A significant reduction in uterine implants were noted following mating between immunised males and control females (p = 0.028), as well as between immunised females and control males (p = 0.004). Histological examination of both the male and female gonads in study week 13 showed atrophy of the seminiferous epithelium and suppression of folliculogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Western
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • Fertility / immunology*
  • Fertilization in Vitro
  • Gonadotropin-Releasing Hormone / genetics*
  • Gonadotropin-Releasing Hormone / immunology*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Molecular Sequence Data
  • Ovary / cytology
  • Ovary / drug effects
  • Plasmids / immunology*
  • Protein Engineering
  • Protein Precursors / genetics*
  • Protein Precursors / immunology*
  • Rats
  • Rats, Sprague-Dawley
  • Sperm Count
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Testis / cytology
  • Testis / drug effects
  • Testosterone / blood
  • Vaccines, Contraceptive / immunology*
  • Vaccines, DNA / immunology
  • Vaccines, Synthetic / immunology

Substances

  • Epitopes, T-Lymphocyte
  • Protein Precursors
  • Vaccines, Contraceptive
  • Vaccines, DNA
  • Vaccines, Synthetic
  • progonadoliberin I
  • Gonadotropin-Releasing Hormone
  • Testosterone