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

M.A.H. Khan, V.A. Ferro, M. Koyama, Y. Kinugasa, M. Song, K. Ogita, Y. Murata, T. Kimura

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)3544-3553
Number of pages10
JournalVaccine
Volume25
Issue number18
DOIs
Publication statusPublished - 4 May 2007

Keywords

  • in vivo fertility
  • anti-GnRH-I antibody
  • GnRH-I vaccine

Cite this