title: Active immunisation of mice with GnRH lipopeptide vaccine candidates: Importance of T helper or multi-dimer GnRH epitope.
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.
authors: The School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia 4072, Queensland, Australia.
authors: Daryn
authors: D
authors: Goodwin
authors: The School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia 4072, Queensland, Australia.
authors: Pavla
authors: P
authors: Simerska
authors: The School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia 4072, Queensland, Australia.
authors: Cheng-Hung
authors: CH
authors: Chang
authors: The School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia 4072, Queensland, Australia.
authors: Friederike M
authors: FM
authors: Mansfeld
authors: The School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia 4072, Queensland, Australia.
authors: Pegah
authors: P
authors: Varamini
authors: The Faculty of Agriculture and Environment, The University Sydney, Camden 2570, New South Wales, Australia.
authors: Michael J
authors: MJ
authors: D'Occhio
authors: The School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia 4072, Queensland, Australia; The School of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, Woolloongabba 4102, Queensland, Australia. Electronic address: i.toth@uq.edu.au.
authors: Istvan
authors: I
authors: Toth
mesh_terms: D000818:Animals; D000939:Epitopes / Q000276:immunology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000276:immunology*; D055666:Lipopeptides / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014611:Vaccination; D014612:Vaccines / Q000276:immunology*
chemical_list: D000939:Epitopes; D055666:Lipopeptides; D014612:Vaccines; D007987:Gonadotropin-Releasing Hormone
keywords: Gonadotropin releasing hormone; Lipopeptide; Murine immunogenicity; T helper; Vaccine