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

作者信息

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

机构信息

The School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia 4072, Queensland, Australia.

The Faculty of Agriculture and Environment, The University Sydney, Camden 2570, New South Wales, Australia.

出版信息

Bioorg Med Chem. 2014 Sep 1;22(17):4848-54. doi: 10.1016/j.bmc.2014.06.052. Epub 2014 Jul 1.

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.

摘要

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