Plasmid DNA vaccine coding eight repeats of gonadotrophin-releasing hormone induced atrophy of prostate in male mice

Abstract

Background: Prostate hyperplasia and neoplasia are major illness of men and elderly dogs. Treatment of prostate cancer requires androgen deprivation surgery or therapy to prevent metastases and alleviate pain. Recently, six DNA vaccines have entered clinical trials against prostate cancer in humans with limited success. There is a need for new therapies that delay the establishment of malignancy and prolong survival. Materials and methods: A plasmid DNA vaccine coding for eight gonadotrophin-releasing hormone (GnRH-I) interspersed in eight T-helper epitopes was used. Sexually mature male mice were immunized with the vaccine in hemagglutinating virus of Japanese envelope vector and boosted in nonionized surfactant vesicles in study weeks 0, 3, 6, 9, and 12. Plasma anti-GnRH-I antibody response, serum testosterone concentration, and effect on prostate were evaluated. Results: Results of an indirect enzyme linked immunosorbent assay (ELISA) showed anti-GnRH-I antibody response (OD value) detected in the study week 3 (0.613 ± 0.179) with a highest response in the week 12 (1.205 ± 0.219). Serum testosterone concentration (ng/ml) in vaccinated mice was significantly reduced (P > 0.000, 0.761 ± 0.531) in the study week 24 in contrast to control serum (7.583 ± 1.251). Group average gross combined weight of prostate and seminal vesicles of vaccinated mice was significantly (P < 0.000) reduced in the study week 24 (319.75 ± 89.19 mg) in contrast to control weight (563.25 ± 108.60 mg). Sections of prostate stained with Goldner's trichrome showed profuse pink color secretion in control tubules, which however was absent in the vaccinated prostate. The lining epithelium of the vaccinated prostate was atrophied and did not enfold in its lumen. Conclusions: Immunization strategy designed with the plasmid DNA vaccine in hemagglutinating virus of Japanese envelope and nonionized surfactant vesicles can be the genetic immunization platform. This vaccine bears potentials in terms of reducing serum testosterone concentration and induction of atrophy of prostate. Targeted ablation of native GnRH-I by genetic immunization could offer leverage to vaccinologists, seeking therapeutic target to control and prevent malignancy of prostate. Keywords: Atrophy of prostate, GnRH-I, Mice, Plasmid DNA vaccine, Serum testosterone