Influence of Carrier Protein Conjugation Site and Terminal Modification of a GnRH-I Peptide Sequence in the Development of a Highly Specific Anti-fertility Vaccine. Part I


Address reprint requests to Dr Valerie A. Ferro, Department of Immunology, University of Strathclyde, SIBS Building, 27 Taylor Street, Glasgow G4 ONR, UK.


PROBLEM: We previously immunoneutralized gonadotrophin releasing hormone (GnRH), using an analogue of GnRH (des-1 GnRH-I), conjugated to tetanus toxoid via a carbodiimide reaction. The castration effect on the reproductive system was not consistent in all the treated animals. Therefore, we examined the possibility that conjugation to the carrier protein via the N- or C-terminal could have an effect on efficacy.

METHOD OF STUDY: GnRH analogue sequences were synthesized consisting of an additional cysteine at either terminal and specific conjugation was carried out using a bifunctional linker agent.

RESULTS: Conjugation of the monomer through the N-terminal proved to be a highly effective means of causing immunocastration in terms of decreased gonadotrophin and testosterone concentrations and testicular size, whereas conjugation through the C-terminal proved to be ineffective. This was reflected in the ability of the antibodies to bind native GnRH, but not the levels of the anti-GnRH antibodies.

CONCLUSION: Immunoneutralization efficacy was attributed to the importance of preserving the GnRH C-terminal.