Enhanced Th۱ and Th۲ immune response induction by Human Papilloma virus Type ۱۶ E۷ DNA vaccine in a tumoric murine model

Background and Objectives: Human papilloma virus (HPV) is known as the etiologic agent of cervical cancer and second common cancer among women. HPV viruses with the elevated risk of infection have more potentiality to cause cancer. The carcinogenesis in these viruses is accomplished by oncoproteins such as E۷. Employing DNA vaccines which code specific antigens such as E۷ is a novel therapeutic approach against such cancers. Methods: In the present study, plasmid coding HPV۱۶ E۷ was administered intracutaneously to C۵۷BL/۶ tumoric mice models for investigation of its immunostimulating potential. PcDNA۳.۱+ vector was used as control vector. After immunization, spleen of animals were removed. Then, release of lactate dehydrogenase (LDH) was evaluated to address the cytotoxic activity (CTL) induced by cellular immunity in spleenocytes. Interferon-γ (IFN-γ) and interleukin-۴ (IL-۴) cytokines were also analyzed as profiles of Th۱ and Th۲, respectively. Anti-inflammatory cytokine interleukin-۱۰ (IL-۱۰) levels were also investigated in tumor microenvironments. Results: Our results showed that CTL activity was higher among samples receiving HPV۱۶ E۷ coding vector in comparison to the group receiving pcDNA۳.۱+ control vector (P < ۰.۰۵). Levels of IFN-γ and IL-۴ were also higher in the group receiving HPV۱۶ E۷ plasmid in comparison to the control group (P < ۰.۰۵). Similarly, IL-۱۰ levels were significantly lower in tumor carrying mice groups receiving HPV۱۶ DNA vaccine compare to PBS and pcDNA۳.۱ receiving control groups. Conclusion: HPV۱۶ E۷ expressing DNA vaccine could increase the release of LDH due to immune system CTL activity. Elevation in IFN-γ and IL-۴ levels as well as IL-۱۰ reduction indicates an increase in both Th۱ and Th۲ profiles resulted by using potent DNA vaccine coding HPV۱۶ E۷ in tumor animal model.