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


METHODS
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.
Ferro
Valerie A
VA
Department of Immunology, University of Strathclyde, Glasgow, UK. v.a.ferro@strath.ac.uk
Harvey
Michael J A
MJ
Colston
Angela
A
Stimson
William H
WH
D000595:Amino Acid Sequence; D000818:Animals; D000915:Antibody Affinity; D000918:Antibody Specificity; D001284:Atrophy; D019281:Dimerization; D004797:Enzyme-Linked Immunosorbent Assay; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000276:immunology; D006727:Hormone Antagonists / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000276:immunology; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D010446:Peptide Fragments / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013091:Spermatogenesis / Q000187:drug effects; D013329:Structure-Activity Relationship; D013737:Testis / Q000187:drug effects / Q000473:pathology; D013739:Testosterone / Q000097:blood; D022642:Vaccines, Contraceptive / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology
C473155:GPRLGYSWHCCHWSYGLRPG-NH2; C473156:HWSYGLRPGCCGPRLGYSWH; D006727:Hormone Antagonists; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D009842:Oligopeptides; D010446:Peptide Fragments; D022642:Vaccines, Contraceptive; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone