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Immunisation of male mice with a plasmid DNA vaccine encoding gonadotrophin releasing hormone (GnRH-I) and t-helper epitopes suppresses fertility in vivo

Khan, M.A.H. and Ferro, V.A. and Koyama, M. and Kinugasa, Y. and Song, M. and Ogita, K. and Murata, Y. and Kimura, T. (2007) Immunisation of male mice with a plasmid DNA vaccine encoding gonadotrophin releasing hormone (GnRH-I) and t-helper epitopes suppresses fertility in vivo. Vaccine, 25 (18). pp. 3544-3553. ISSN 0264-410X

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Abstract

Immunisation against mammalian gonadotrophin releasing hormone (GnRH-I) linked to large carrier proteins has been shown to disrupt fertility. However, various studies have shown that the carrier protein causes epitope suppression of the hapten response, resulting in short-lived immunoneutralisation, followed by a return of fertility. A range of strategies has been used to resolve this, with limited success. The aim of this study was to construct a plasmid DNA vaccine encoding GnRH-I and T-helper epitopes. A 498 bp long vaccine construct in pcDNA3.1+ was administered to male mice in conjunction with a Hemagglutinating Virus of Japanese Envelop (HVJ-E) vector or in saline solution. The vaccine efficacy was evaluated in terms of GnRH-I specific IgG antibody response, serum testosterone levels, testicular spermatogenesis and the ability to produce offspring. The vaccine appeared to induce higher anti-GnRH-I IgG antibody response and insult the fertility axis, which was characterised by a drop of epididymal sperm counts, reduction of serum testosterone levels, suppressed testicular spermatogenesis and a significant decrease in litter numbers compared to control animals. The end-point vaccine efficacy was much higher in the HVJ-E vector mediated immunisation, than in saline alone.