Enhanced Th1 and Th2 immune response induction by Human Papilloma virus Type 16 E7 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 E7. Employing DNA vaccines which code specific antigens such as E7 is a novel therapeutic approach against such cancers. Methods: In the present study, plasmid coding HPV16 E7 was administered intracutaneously to C57BL/6 tumoric mice models for investigation of its immunostimulating potential. PcDNA3.1+ 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-4 (IL-4) cytokines were also analyzed as profiles of Th1 and Th2, respectively. Anti-inflammatory cytokine interleukin-10 (IL-10) levels were also investigated in tumor microenvironments. Results: Our results showed that CTL activity was higher among samples receiving HPV16 E7 coding vector in comparison to the group receiving pcDNA3.1+ control vector (P < 0.05). Levels of IFN-γ and IL-4 were also higher in the group receiving HPV16 E7 plasmid in comparison to the control group (P < 0.05). Similarly, IL-10 levels were significantly lower in tumor carrying mice groups receiving HPV16 DNA vaccine compare to PBS and pcDNA3.1 receiving control groups. Conclusion: HPV16 E7 expressing DNA vaccine could increase the release of LDH due to immune system CTL activity. Elevation in IFN-γ and IL-4 levels as well as IL-10 reduction indicates an increase in both Th1 and Th2 profiles resulted by using potent DNA vaccine coding HPV16 E7 in tumor animal model.