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

Khan, Muhammad A.H. and Ogita, Kazuhide and Ferro, V.A. and Kumasawa, Keiichi and Tsutsui, Takeki and Kimura, Tadashi (2008) Immunisation with a plasmid DNA vaccine encoding gonadotrophin releasing hormone (GnRH-I) and T-helper epitopes in saline suppresses rodent fertility. Vaccine, 26 (10). pp. 1365-1374. ISSN 0264-410X

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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 μg/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.