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:: Volume 4, Number 2 (Autumn & Winter 2016 2017) ::
Hakim Jorjani J 2017, 4(2): 58-67 Back to browse issues page
Enhanced Th1 and Th2 immune response induction by Human Papilloma virus Type 16 E7 DNA vaccine in a tumoric murine model
Alireza Mohebbi, Sanaz Baghban Rahimi, Alijan Tabarraei, Mohsen Saeedi, Mirsaeed Ebrahimzadeh, Leila Alizadeh, Amir Ghaemi
Infectious Disease Research Center, Department of Microbiology, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran , Ghaem_amir@yahoo.com
Abstract:   (734 Views)

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.

Keywords: E7 DNA vaccine, Human papillomavirus, cytokine, cellular immunity, cervical cancer
Full-Text [PDF 638 kb]   (286 Downloads)    
Type of Study: Original paper | Subject: General
Received: 2016/12/26 | Accepted: 2016/12/26 | Published: 2016/12/26
References
1. de Sanjosé S, Diaz M, Castellsagué X, Clifford G, Bruni L, Muñoz N, et al. Worldwide prevalence and genotype distribution of cervical human papillomavirus DNA in women with normal cytology: a meta-analysis. The Lancet Infectious Diseases. 2007;7(7):453-9
2. Bosch F, Lorincz A, Munoz N, Meijer C, Shah K. The causal relation between human papillomavirus and cervical cancer. Journal of clinical pathology. 2002;55(4):244-65
3. Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. The Journal of pathology. 1999;189(1):12-9
4. Gillison ML. Human papillomavirus-associated head and neck cancer is a distinct epidemiologic, clinical, and molecular entity. Seminars in oncology. 2004;31(6):744-54
5. Lowy DR, Schiller JT. Prophylactic human papillomavirus vaccines. Journal of Clinical Investigation. 2006;116(5):1167-73
6. Hung C-F, Ma B, Monie A, Tsen S-W, Wu TC. Therapeutic human papillomavirus vaccines: current clinical trials and future directions. Expert opinion on biological therapy. 2008;8(4):421-39
7. Stanley MA. Genital human papillomavirus infections: current and prospective therapies. The Journal of general virology. 2012;93(Pt 4):681-91
8. Monie A, Tsen S-WD, Hung C-F, Wu TC. Therapeutic HPV DNA vaccines. Expert review of vaccines. 2009;8(9):1221-35
9. McLaughlin-Drubin ME, Münger K. The Human Papillomavirus E7 Oncoprotein. Virology. 2009;384(2):335-44
10. Liu X, Clements A, Zhao K, Marmorstein R. Structure of the human Papillomavirus E7 oncoprotein and its mechanism for inactivation of the retinoblastoma tumor suppressor. Journal of Biological Chemistry. 2006;281(1):578-86
11. Tindle RW. Immune evasion in human papillomavirus-associated cervical cancer. Nat Rev Cancer. 2002;2(1):59-64
12. Ferraro B, Morrow MP, Hutnick NA, Shin TH, Lucke CE, Weiner DB. Clinical applications of DNA vaccines: current progress. Clinical infectious diseases. 2011;53(3):296-302
13. Lara AR, Ramirez OT, Wunderlich M. Plasmid DNA production for therapeutic applications. Methods in molecular biology (Clifton, NJ). 2012;824:271-303
14. Lin K, Roosinovich E, Ma B, Hung CF, Wu TC. Therapeutic HPV DNA vaccines. Immunologic research. 2010;47(1-3):86-112
15. Tahamtan A, Ghaemi A, Gorji A, Kalhor HR, Sajadian A, Tabarraei A, et al. Antitumor effect of therapeutic HPV DNA vaccines with chitosan-based nanodelivery systems. Journal of biomedical science. 2014;21:69
16. Ghaemi A, Soleimanjahi H, Gill P, Hassan Z, Jahromi SR, Roohvand F. Recombinant lambda-phage nanobioparticles for tumor therapy in mice models. Genetic vaccines and therapy. 2010;8:3
17. Lissat A, Joerschke M, Shinde DA, Braunschweig T, Meier A, Makowska A, et al. IL6 secreted by Ewing sarcoma tumor microenvironment confers anti-apoptotic and cell-disseminating paracrine responses in Ewing sarcoma cells. BMC cancer. 2015;15:552
18. Trimble CL, Morrow MP, Kraynyak KA, Shen X, Dallas M, Yan J, et al. Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3: a randomised, double-blind, placebo-controlled phase 2b trial. The Lancet.386(10008):2078-88
19. Morrow M, Trimble C, Shen X, Dallas M, Weiner D, Boyer J, et al. Abstract CT131: HPV specific immunotherapy for cervical intraepithelial neoplasia using VGX-3100 induces regression of cervical lesions and potent T-cell responses: Results from a randomized, double-blind, placebo-controlled phase II study. Cancer research. 2015;75(15 Supplement):CT131-CT
20. Bradley LM, Dalton DK, Croft M. A direct role for IFN-gamma in regulation of Th1 cell development. Journal of immunology. 1996;157(4):1350-8
21. Cope A, Le Friec G, Cardone J, Kemper C. The Th1 life cycle: molecular control of IFN-gamma to IL-10 switching. Trends in immunology. 2011;32(6):278-86
22. Eskdale J, Kube D, Tesch H, Gallagher G. Mapping of the human IL10 gene and further characterization of the 5' flanking sequence. Immunogenetics. 1997;46(2):120-8
23. Aste-Amezaga M, Ma X, Sartori A, Trinchieri G. Molecular mechanisms of the induction of IL-12 and its inhibition by IL-10. Journal of immunology (Baltimore, Md : 1950). 1998;160(12):5936-44
24. Sokol CL, Barton GM, Farr AG, Medzhitov R. A Mechanism for the Initiation of the Th2 Response by an Allergen. Nature immunology. 2008;9(3):310-8
25. Ghaemi A, Soleimanjahi H, Gill P, Hassan ZM, Razeghi S, Fazeli M, et al. Protection of mice by a lambda-based therapeutic vaccine against cancer associated with human papillomavirus type 16. Intervirology. 2011;54(3):105-12
26. Bahrami AA, Ghaemi A, Tabarraei A, Sajadian A, Gorji A, Soleimanjahi H. DNA vaccine encoding HPV-16 E7 with mutation in L-Y-C-Y-E pRb-binding motif induces potent anti-tumor responses in mice. J Virol Methods. 2014;206:12-8
27. Sajadian A, Tabarraei A, Soleimanjahi H, Fotouhi F, Gorji A, Ghaemi A. Comparing the effect of Toll-like receptor agonist adjuvants on the efficiency of a DNA vaccine. Archives of virology. 2014;159(8):1951-60
28. Tahamtan A, Ghaemi A, Gorji A, Kalhor HR, Sajadian A, Tabarraei A, et al. Antitumor effect of therapeutic HPV DNA vaccines with chitosan-based nanodelivery systems. Journal of Biomedical Science. 2014;21(1):69
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Mohebbi A, Baghban Rahimi S, Tabarraei A, Saeedi M, Ebrahimzadeh M, Alizadeh L et al . Enhanced Th1 and Th2 immune response induction by Human Papilloma virus Type 16 E7 DNA vaccine in a tumoric murine model. Hakim Jorjani J. 2017; 4 (2) :58-67
URL: http://goums.ac.ir/jorjanijournal/article-1-475-en.html
Volume 4, Number 2 (Autumn & Winter 2016 2017) Back to browse issues page
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