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.

LanguageEnglish
Pages372-380
Number of pages9
JournalAmerican Journal of Reproductive Immunology
Volume48
Issue number6
DOIs
Publication statusPublished - 9 Dec 2002

Fingerprint

Contraceptive Vaccines
Dimerization
Gonadotropin-Releasing Hormone
Tetanus Toxoid
Castration
Peptides
Antibody Affinity
Neutralizing Antibodies
Antibody Formation
Sprague Dawley Rats
Testosterone
Antibodies

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

Cite this

@article{e1c050eb2a634dc08279ed1666af8e85,
title = "Part II: influence of dimerization of a modified GnRH-I peptide sequence on a male antifertility vaccine",
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.",
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",
author = "Ferro, {Valerie A.} and Harvey, {Michael J. A.} and Angela Colston and Stimson, {William H.}",
year = "2002",
month = "12",
day = "9",
doi = "10.1034/j.1600-0897.2002.01121.x",
language = "English",
volume = "48",
pages = "372--380",
journal = "American Journal of Reproductive Immunology",
issn = "1046-7408",
number = "6",

}

Part II : influence of dimerization of a modified GnRH-I peptide sequence on a male antifertility vaccine. / Ferro, Valerie A.; Harvey, Michael J. A.; Colston, Angela; Stimson, William H.

In: American Journal of Reproductive Immunology, Vol. 48, No. 6, 09.12.2002, p. 372-380.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Part II

T2 - American Journal of Reproductive Immunology

AU - Ferro, Valerie A.

AU - Harvey, Michael J. A.

AU - Colston, Angela

AU - Stimson, William H.

PY - 2002/12/9

Y1 - 2002/12/9

N2 - 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.

AB - 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.

KW - amino acid sequence

KW - animals

KW - antibody affinity

KW - antibody specificity

KW - atrophy

KW - dimerization

KW - enzyme-linked immunosorbent assay

KW - follicle stimulating hormone

KW - gonadotropin-releasing hormone

KW - hormone antagonists

KW - immunization

KW - immunoglobulin G

KW - immunoglobulin M

KW - luteinizing hormone

KW - male

KW - molecular sequence data

KW - oligopeptides

KW - organ size

KW - peptide fragments

KW - rats

KW - rats, sprague-dawley

KW - spermatogenesis

KW - structure-activity relationship

KW - testis

KW - testosterone

KW - vaccines, contraceptive

UR - http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1600-0897

U2 - 10.1034/j.1600-0897.2002.01121.x

DO - 10.1034/j.1600-0897.2002.01121.x

M3 - Article

VL - 48

SP - 372

EP - 380

JO - American Journal of Reproductive Immunology

JF - American Journal of Reproductive Immunology

SN - 1046-7408

IS - 6

ER -