Active immunisation of mice with GnRH lipopeptide vaccine candidates: Importance of T helper or multi-dimer GnRH epitope

Daryn Goodwin, Pavla Simerska, Cheng Hung Chang, Friederike M. Mansfeld, Pegah Varamini, Michael J. D'Occhio, Istvan Toth

Research output: Contribution to journalArticleResearchpeer-review

10 Citations (Scopus)

Abstract

Active immunisation against gonadotropin releasing hormone (GnRH) is a potential alternative to surgical castration. This study focused on the development of a GnRH subunit lipopeptide vaccine. A library of vaccine candidates that contained one or more (up to eight) copies of monomeric or dimeric GnRH peptide antigen, an adjuvanting lipidic moiety based on lipoamino acids, and an additional T helper epitope, was synthesised by solid phase peptide synthesis. The candidates were evaluated in vivo in order to determine the minimal components of this vaccine necessary to induce a systemic immune response. BALB/c mice were immunised with GnRH lipopeptide conjugates, co-administered with or without Complete Freund's Adjuvant, followed by two additional immunisations. Significant GnRH-specific IgG titres were detected in sera obtained from mice immunised with four of the seven lipopeptides tested, with an increase in titres observed after successive immunisations. This study highlights the importance of for epitope optimisation and delivery system design when producing anti-hapten antibodies in vivo. The results of this study also contribute to the development of future clinical and veterinary immunocontraceptives.

Original languageEnglish
Pages (from-to)4848-4854
Number of pages7
JournalBioorganic & Medicinal Chemistry
Volume22
Issue number17
DOIs
Publication statusPublished - 1 Sep 2014
Externally publishedYes

Keywords

  • Gonadotropin releasing hormone
  • Lipopeptide
  • Murine immunogenicity
  • T helper
  • Vaccine

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