Immunisation of male mice with a plasmid DNA vaccine encoding gonadotrophin releasing hormone (GnRH-I) and T-helper epitopes suppresses fertility in vivo

• Published in: Vaccine 2007-05, Vol.25 (18), p.3544-3553
• Main Authors: Khan, Mohammad A.H, Ferro, Valerie A, Koyama, Shinsuke, Kinugasa, Yukiko, Song, Mihyon, Ogita, Kazuhide, Tsutsui, Tateki, Murata, Yuji, Kimura, Tadashi
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Amino Acid Sequence; Animals; Anti-GnRH-I antibody; Antibody Specificity; Applied microbiology; Base Sequence; Biological and medical sciences; Contraception, Immunologic; Epitopes, T-Lymphocyte - chemistry; Epitopes, T-Lymphocyte - genetics; Epitopes, T-Lymphocyte - immunology; Female; Fertility - drug effects; Fundamental and applied biological sciences. Psychology; GnRH-I vaccine; Gonadotropin-Releasing Hormone - genetics; Gonadotropin-Releasing Hormone - immunology; Hemagglutinating virus of Japan; Immunization - methods; Immunoglobulin G - blood; In vivo fertility; Litter Size - drug effects; Male; Mice; Mice, Inbred ICR; Microbiology; Molecular Sequence Data; Plasmids - genetics; Spermatogenesis - drug effects; T-Lymphocytes, Helper-Inducer - immunology; Testosterone - blood; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Contraceptive; Vaccines, DNA - administration & dosage; Vaccines, DNA - immunology
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2007.01.089

Abstract 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.