Immunization of Female Mice with a Plasmid DNA Vaccine Coding EightRepeats of Gonadotrophin Releasing Hormone (Gnrh-I) and Eight T-HelperEpitopes Suppress Fertility In Vivo

Rima, Umme and Kimura, Tadashi and Gebril, Ayman M and Islam, Mohammad and Bari, Abu and Ferro, Valerie and Khan, Mohammad (2015) Immunization of Female Mice with a Plasmid DNA Vaccine Coding EightRepeats of Gonadotrophin Releasing Hormone (Gnrh-I) and Eight T-HelperEpitopes Suppress Fertility In Vivo. Journal of Vaccines and Vaccination, 6 (3). ISSN 2157-7560

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    Abstract

    Induction of an appropriate immune response against gonadotrophin releasing hormone (GnRH-I) disrupt fertility,reduce fecundity and regress tumours of reproductive system.To disrupt fertility a plasmid DNA vaccine wasengineered coding eight repeats of GnRH-I and eight T-helper epitopes. Translation efficiency of the vaccine wasevaluated in undifferentiated COS1 cells and found to release GnRH-I fusion protein in culture supernatant. Swissalbino female mice (N=24) were immunized with 50μg plasmid DNA construct in study weeks 0, 3, 6, 9 and 12.Group 2 mice were primed with the plasmid DNA in hemagglutinating virus of japanese envelope (HVJE) vector andsubsequent boosts were carried out in phosphate buffer saline. Group 3 mice were immunized with the plasmid DNAin non-ionic surfactant vesicles (NISV) and Group 1 was served as untreated control. The effect of immunization wasstudied in terms of anti-GnRH-I antibody response (OD value at A540 ± SD), suppression of ovarian folliculogenesis,altered uterine histoarchitecture and impaired fertility in vivo in mating trials. In study week 24 OD values of anti-GnRH-I antibody response were 0.982 ± 0.231 in Group 3 mice, followed by 0.783 ± 0.191 in Group 2 in comparisonwith no response in Group 1 controls (0.237 ± 0.147). Results of mating trials showed conception failure invaccinated mice; 51, 18 and 05 pups were seen in the uteri of Groups 1, 2 and 3 mice respectively. There wassignificant (p>0.001) reduction in the weight of ovaries in Group 2 (8.50 ± 2.38 mg) and Group 3 (7.25 ± 0.95 mg)mice compared to Group 1 control (15.00 ± 1.41 mg). Significant reduction of ovarian folliculogenesis was seen inGroup 2 (p>0.001) and Group 3 mice (p>0.01). In conclusion, the plasmid DNA vaccine delivered in female micewith HVJE and NISV induced significantly (p>0.001) higher levels of anti-GnRH-I antibody response, suppressedovarian and uterine function and impaired fertility in vivo.