Immunisation of male mice with a plasmid DNA vaccine encoding gonadotrophin releasing hormone (GnRH-I) and T-helper epitopes suppresses fertility in vivo.
Immunisation against mammalian gonadotrophin releasing hormone (GnRH-I) linked to large carrier proteins has been shown to disrupt fertility. However, various studies have shown that the carrier protein causes epitope suppression of the hapten response, resulting in short-lived immunoneutralisation, followed by a return of fertility. A range of strategies has been used to resolve this, with limited success. The aim of this study was to construct a plasmid DNA vaccine encoding GnRH-I and T-helper epitopes. A 498 bp long vaccine construct in pcDNA3.1+ was administered to male mice in conjunction with a Hemagglutinating Virus of Japanese Envelop (HVJ-E) vector or in saline solution. The vaccine efficacy was evaluated in terms of GnRH-I specific IgG antibody response, serum testosterone levels, testicular spermatogenesis and the ability to produce offspring. The vaccine appeared to induce higher anti-GnRH-I IgG antibody response and insult the fertility axis, which was characterised by a drop of epididymal sperm counts, reduction of serum testosterone levels, suppressed testicular spermatogenesis and a significant decrease in litter numbers compared to control animals. The end-point vaccine efficacy was much higher in the HVJ-E vector mediated immunisation, than in saline alone.
Khan
Mohammad A H
MA
Division of Obstetrics and Gynecology, Department of Specific Organ Regulation, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Ferro
Valerie A
VA
Koyama
Shinsuke
S
Kinugasa
Yukiko
Y
Song
Mihyon
M
Ogita
Kazuhide
K
Tsutsui
Tateki
T
Murata
Yuji
Y
Kimura
Tadashi
T
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D001483:Base Sequence; D003269:Contraception, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D005260:Female; D005298:Fertility / Q000187:drug effects*; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics / Q000276:immunology*; D007114:Immunization / Q000379:methods; D007074:Immunoglobulin G / Q000097:blood; D008098:Litter Size / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics; D013091:Spermatogenesis / Q000187:drug effects; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D013739:Testosterone / Q000097:blood; D022642:Vaccines, Contraceptive; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; D022642:Vaccines, Contraceptive; D019444:Vaccines, DNA; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone