Part II: influence of dimerization of a modified GnRH-I peptide sequence on a male antifertility vaccine

Valerie A. Ferro, Michael J. A. Harvey, Angela Colston, William H. Stimson

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

PROBLEM: In the previous paper, we described how the tetanus toxoid (TT) conjugated monomer, CHWSYGLRPG-NH2, induced high neutralizing antibody titres, which resulted in decreased levels of testosterone and subsequent antifertility. However, its counterpart HWSYGLRPGC, induced low avidity antibody titres. We wanted to know whether peptide dimerization would improve the efficacy of both peptides.

METHOD OF STUDY: Male Sprague-Dawley rats were immunized with modified dimerized GnRH-I peptides (HWSYGLRPGCCGPRLGYSWH and GPRLGYSWHCCHWSYGLRPG-NH2), with or without conjugation to TT.

RESULTS: The unconjugated dimers were not effective in causing castration, although the first peptide dimer did induce production of antibodies. When conjugated to TT, both dimers showed the same level of efficacy in causing castration as each other. However, there were differences in antibody binding to native GnRH.

CONCLUSIONS: Dimerization and conjugation to a carrier improved the antifertility efficacy of HWSYGLRPGC, whereas the conjugated monomer CHWSYGLRPG-NH2 showed a greater level of consistent castration than its conjugated dimer.

Original languageEnglish
Pages (from-to)372-380
Number of pages9
JournalAmerican Journal of Reproductive Immunology
Volume48
Issue number6
DOIs
Publication statusPublished - 9 Dec 2002

Keywords

  • amino acid sequence
  • animals
  • antibody affinity
  • antibody specificity
  • atrophy
  • dimerization
  • enzyme-linked immunosorbent assay
  • follicle stimulating hormone
  • gonadotropin-releasing hormone
  • hormone antagonists
  • immunization
  • immunoglobulin G
  • immunoglobulin M
  • luteinizing hormone
  • male
  • molecular sequence data
  • oligopeptides
  • organ size
  • peptide fragments
  • rats
  • rats, sprague-dawley
  • spermatogenesis
  • structure-activity relationship
  • testis
  • testosterone
  • vaccines, contraceptive

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