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

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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 1873-2518 (https://doi.org/10.1016/j.vaccine.2007.01.089)

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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.

ORCID iDs

Khan, M.A.H., Ferro, V.A. ORCID logoORCID: https://orcid.org/0000-0003-1967-3603, Koyama, M., Kinugasa, Y., Song, M., Ogita, K., Murata, Y. and Kimura, T.;
CORE (COnnecting REpositories)