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. 2015 Jan-Feb;8(1):18-23.

Further Stimulation of Cellular Immune Responses through Association of HPV-16 E6, E7 and L1 Genes in order to produce more Effective Therapeutic DNA Vaccines in Cervical Cancer Model

Maryam Fazeli  1 , Hoorieh Soleimanjahi  1 , Simin Dadashzadeh  2
Affiliations

Further Stimulation of Cellular Immune Responses through Association of HPV-16 E6, E7 and L1 Genes in order to produce more Effective Therapeutic DNA Vaccines in Cervical Cancer Model

Maryam Fazeli et al. Iran J Cancer Prev. 2015 Jan-Feb.

Abstract

Background: Cervical cancer has been shown to be highly associated with human papillomavirus (HPV) infection. The viral oncogenes E6 and E7 are constantly expressed by the tumor cells and are therefore potent targets for therapeutic genetic vaccination. In the present study, it was investigated the potential effect of HPV-16 E6, E7 and L1 co-administration to activate specific cytotoxic T lymphocytes in tumor mice models.

Methods: The HPV-16 E6, E7 and L1 genes from Iranian isolate were separately inserted into the mammalian expression vector, pcDNA3, to construct the DNA vaccine candidates. Tumor-bearing Animals (C57BL/6 mice) were immunized with the vaccine candidate; then, Lymphocyte Proliferation Assay (LPA) and relative tumor volume measurements were carried out in order to examine the immunological effects of the vaccine.

Results: Obtained results showed that co-administration of the HPV-16 E6, E7 and L1 DNA induced HPV-16 specific cellular immune responses and also protected against TC-1-induced tumor in vivo compared with negative controls.

Conclusion: The results showed that mixed delivery systems might be valuable to improve the magnitude of the induced immune responses and confirmed therapeutic effects of HPV-16 E6, E7 through cytotoxic T lymphocyte induction and illustrate the new promising role for HPV-16 L1 CTL epitopes as a suitable CTL inducer.

Keywords: immunocellular responses; pcDNA3/E6; pcDNA3/E7; pcDNA3/L1.

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Figures

Figure 1
Figure 1
TC-1 cell line in media culture before counting, and injecting into the left flank of C57BL/6.
Figure 2
Figure 2
Observation of tumor in mice that were inoculated with 106 TC-1 cells.
Figure 3
Figure 3
The stimulation calculated indexes for different vaccinated groups; C57BL/6 mice were injected subcutaneously with TC-1 cells. After two week, the mice were immunized intramuscularly (IM) twice at a two weeks interval with 100 ml phosphate buffered saline (PBS; negative control), 100 mg naked DNA vaccine encoding pcDNA3 (negative plasmid control), pcDNA3/L1, pcDNA3/E6, pcDNA3/E7, pcDNA3/E6 & pcDNA3/E7, pcDNA3/E6 & pcDNA3/L1, pcDNA3/E7 & pcDNA3/L1 and pcDNA3/E6 & pcDNA3/E7 & pcDNA3/L1 in PBS. Two weeks after final immunization, spleen of individual mice (three/group) was removed and lymphocyte proliferation was evaluated using the MTT method. Formazan crystal formation after incubation with MTT was determined by solving the crystals in DMSO, and the OD was read at 540 nm. Lymphocyte proliferation in the pcDNA3/E6 & pcDNA3/E7 & pcDNA3/L1 group was significantly higher than in the other groups especially negative control group (p<0.05).
Figure 4
Figure 4
Assessment of therapeutic vaccine on tumor size between the 4th and 6th weeks after the tumor inoculation
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