واکسنهای نوکلئیک اسیدی برای ویروس پاپیلومای انسان؛ پیشگیری یا درمان

نوع مقاله: مروری

نویسندگان

1 استادیار گروه زیست‌شناسی سلولی و مولکولی، دانشکده علوم پایه، دانشگاه شهید مدنی آذربایجان، تبریز، ایران.

2 دانشجوی کارشناسی ارشد زیست‌شناسی سلولی و مولکولی، دانشکده علوم پایه، دانشگاه شهید مدنی آذربایجان، تبریز، ایران.

چکیده

مقدمه: سرطان رحم، چهارمین سرطان رایج در زنان می­باشد. تقریباً در تمامی موارد این سرطان، ابتلاء به انواع ویروس پاپیلومای انسانی با خطر بالا به‌خصوص تیپ­های 16 و 18 مشاهده می­شود. این ویروس عامل ایجاد سرطان‌های دیگری نظیر اوروفارنکس، آنورکتال و همچنین پوست نیز می­باشد. مطالعه مروری حاضر با هدف بررسی واکسن­های موجود و در حال توسعه برای پیشگیری یا درمان HPV انجام شد.
روش‌کار: در این پژوهش مروری، کلمات کلیدی HPV، سرطان سرویکس، DNA واکسن، RNA واکسن، پیشگیری و درمان آلودگی با HPV در پایگاه­های PubMed، Science direct، Scopus و Google Scholar در بازه زمانی سال­های 2000 تا 2018 مورد جستجو قرار گرفتند. مقالات انگلیسی به‌روز و چاپ شده در مجلات چارک اول، در اولویت قرار گرفتند و مقالات دارای اطلاعات ناقص و نامرتبط از مطالعه حذف شدند.
یافته­ها: با وجود واکسن­هایی برای پیشگیری از ابتلاء به HPV، تحقیقات بر روی ارائه واکسن بهتر بر علیه این ویروس ادامه دارد، زیرا واکسن­های موجود از تمامی تیپ­های پرخطر ویروس پیشگیری نمی­کنند. همچنین بر روی افراد مبتلا و دارای ناهنجاری­های حاصل از ویروس و یا سرطان تأثیری ندارند. از راهکار­های امیدبخش، واکسن­هایی بر اساس نوکلئیک­اسید­ها (DNA یا RNA) می­باشند.
نتیجه­گیری: نوکلئیک­اسید واکسن­ها دارای نتایج امیدوارکننده­ای به دلیل امن بودن، پایداری، راحتی در تولید و توانایی ایجاد ایمنی اختصاصی می­باشند. در حال حاضر واکسن­های GX-188E، VGX-3100، ZNF–603 و ZNF -758 بر علیه ژن­های E6 و E7 ویروس در فاز کلینیکی موفق عمل کرده­اند و امیدهایی برای یک واکسن درمانی برای افراد آلوده به ویروس یا مبتلا به سرطان ایجاد کرده اند.

کلیدواژه‌ها


عنوان مقاله [English]

Nucleic acid vaccines for human papillomavirus; prevention or treatment

نویسندگان [English]

  • Solmaz Moniri Javadhesari 1
  • Sepehr Pourseif 2
  • Keyvan Khakpour 2
1 Assistant Professor, Department of Molecular and Cellular Biology, School of Basic Sciences, Azarbaijan Shahid Madani University, Tabriz, Iran.
2 M.Sc. student of Molecular and Cellular Biology, School of Basic Sciences, Azarbaijan Shahid Madani University, Tabriz, Iran.
چکیده [English]

Introduction: Cervical cancer is the fourth common cancer among women. In almost all cases of this cancer, infection to a high risk human papilloma virus (HPV) especially type 16 and 18 is observed. HPV is also the cause of other cancers such as oropharyngeal, anorectal and skin. This study was performed with aim to evaluate the vaccines available or under investigation to prevent or treat HPV infection.
Methods: In this review study, the keywords of HPV, cervix cancer, DNA vaccine, RNA vaccine, and prevention or treatment of HPV infections were searched in databases of PubMed, Science direct, Scopus and Google Scholar from 2000 to 2018. The recent articles published in English Q1 journals were selected, and the articles with incomplete or irrelevant data were excluded from the study. 
Results: Despite the available vaccines to prevent HPV infection, ongoing research is continued to develop assorted vaccines against it, because available vaccines don’t prevent all high risk types of HPV; also they are not effective on those who are already infected and have HPV associated malignancies or cancer. Nucleic acid based (DNA or RNA) vaccines are of promising approaches.
Conclusion:Nucleic acid vaccines have promising outcomes due to safety, stability, simplicity of providing and ability to induce antigen-specific immunity. Currently, GX-188E, VGX-3100, ZNF–603 and ZNF -758 vaccines are successfully passing clinical trials based on E6 and E7 genes of HPV. These vaccines caused hopes for a vaccine to treat those who are already infected or have cancer.

کلیدواژه‌ها [English]

  • Cervical Cancer
  • DNA Vaccines
  • Human papillomavirus
  • RNA Vaccines
  • Therapeutic vaccines
  1. Zhou HL, Zhang W, Zhang CJ, Wang SM, Duan YC, Wang JX, et al. Prevalence and distribution of human papillomavirus genotypes in Chinese women between 1991 and 2016: a systematic review. J Infect 2018; 76(6):522-8.
  2. Chabeda A, Yanez RJ, Lamprecht R, Meyers AE, Rybicki EP, Hitzeroth II. Therapeutic vaccines for high-risk HPV-associated diseases. Papillomavirus Res 2018; 5:46-58.
  3. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Meeting, World Health Organization, International Agency for Research on Cancer. Human papillomaviruses. Geneva: World Health Organization; 2007.
  4. Shanmugasundaram S, You J. Targeting persistent human papillomavirus infection. Viruses 2017; 9(8):229.
  5. Malakouti J, Mirghafourvand M, Gorbani M, Salehi Poormehr H, Pourasad Shahrak S, Jafari Shabiri M. Incidence of Human Papilloma Virus (HPV) infection and its relevant factors among women referring to Alzahra Therapeutic-Educational Center of Tabriz, September 2013 to March 2014. Iran J Obstet Gynecol Infertil 2016; 18(185):16-22. (Persian).
  6. Choi YJ, Park JS. Clinical significance of human papillomavirus genotyping. J Gynecol Oncol 2015; 27(2):e21.
  7. Sohrabi A, Rahnamaye Farzami M, Mirab Samiee S, Modarresi MH. An overview on papillomaviruses as the main cause of cervical cancer. Iran J Obstet Gynecol Infertil 2015; 18(145):14-25. (Persian).
  8. Campo MS, Roden RB. Papillomavirus prophylactic vaccines: established successes, new approaches. J Virol 2010; 84(3):1214-20.
  9. Roden RB, Stern PL. Opportunities and challenges for human papillomavirus vaccination in cancer. Nat Rev Cancer 2018; 18(4):240.
  10. Evans MR, James CD, Bristol ML, Nulton TJ, Wang X, Kaur N, et al. Human papillomavirus 16 E2 regulates keratinocyte gene expression relevant to cancer and the viral life cycle. J Virol 2019; 93(4):e01941-18.
  11. Vici P, Pizzuti L, Mariani L, Zampa G, Santini D, Di Lauro L, et al. Targeting immune response with therapeutic vaccines in premalignant lesions and cervical cancer: hope or reality from clinical studies. Expert Rev Vaccines 2016; 15(10):1327-36.
  12. Schiller JT, Castellsagué X, Garland SM. A review of clinical trials of human papillomavirus prophylactic vaccines. Vaccine 2012; 30(Suppl 5):F123-38.
  13. Ma B, Maraj B, Tran NP, Knoff J, Chen A, Alvarez RD, et al. Emerging human papillomavirus vaccines Expert Opin Emerg Drugs 2012; 17(4):469-92.
  14. Hasanzadeh Mofrad M, Jedi L, Ahmadi S. The role of Human Papilloma Virus (HPV) vaccines in prevention of Cervical Cancer, review article. Iran J Obstet Gynecol Infertil 2016; 19(21):22-9. (Persian).
  15. Deschuyteneer M, Elouahabi A, Plainchamp D, Plisnier M, Soete D, Corazza Y, et al. Molecular and structural characterization of the L1 virus-like particles that are used as vaccine antigens in Cervarix™, the AS04-adjuvanted HPV-16 and-18 cervical cancer vaccine. Hum Vaccines 2010; 6(5):407-19.
  16. Hung CF, Ma B, Monie A, Tsen SW, Wu TC. Therapeutic human papillomavirus vaccines: current clinical trials and future directions. Expert Opin Biol Ther 2008; 8(4):421-39.
  17. Cheng MA, Farmer E, Huang C, Lin J, Hung CF, Wu TC. Therapeutic DNA vaccines for human papillomavirus and associated diseases. Hum Gene Ther 2018; 29(9):971-96.
  18. Monie A, Tsen SW, Hung CF, Wu TC. Therapeutic HPV DNA vaccines. Expert Rev Vaccines 2009; 8(9):1221-35.
  19. Pierini S, Perales-Linares R, Uribe-Herranz M, Pol JG, Zitvogel L, Kroemer G, et al. Trial watch: DNA-based vaccines for oncological indications. Oncoimmunology 2017; 6(12):e1398878.
  20. Bourla AB, Zamarin D. Immunotherapy: new strategies for the treatment of gynecologic malignancies. Oncology 2016; 30(1):59.
  21. Yang A, Farmer E, Wu TC, Hung CF. Perspectives for therapeutic HPV vaccine development. J Biomed Sci 2016; 23(1):75.
  22. Lee SJ, Yang A, Wu TC, Hung CF. Immunotherapy for human papillomavirus-associated disease and cervical cancer: review of clinical and translational research. J Gynecol Oncol 2016; 27(5):e51.
  23. Lin K, Roosinovich E, Ma B, Hung CF, Wu TC. Therapeutic hpv DNA vaccines. Immunol Res 2010; 47(1-3):86-112.
  24. Alvarez RD, Huh WK, Bae S, Lamb Jr LS, Conner MG, Boyer J, et al. A pilot study of pNGVL4a-CRT/E7 (detox) for the treatment of patients with HPV16+ cervical intraepithelial neoplasia 2/3 (CIN2/3). Gynecol Oncol 2016; 140(2):245-52.
  25. Widera G, Austin M, Rabussay D, Goldbeck C, Barnett SW, Chen M, et al. Increased DNA vaccine delivery and immunogenicity by electroporation in vivo. J Immunol 2000; 164(9):4635-40.
  26. Zeira E, Manevitch A, Manevitch Z, Kedar E, Gropp M, Daudi N, et al. Femtosecond laser: a new intradermal DNA delivery method for efficient, long-term gene expression and genetic immunization. FASEB J 2007; 21(13):3522-33.
  27. Klencke B, Matijevic M, Urban RG, Lathey JL, Hedley ML, Berry M, et al. Encapsulated plasmid DNA treatment for human papillomavirus 16-associated anal dysplasia: a Phase I study of ZYC101. Clin Cancer Res 2002; 8(5):1028-37.
  28. Garcia F, Petry KU, Muderspach L, Gold MA, Braly P, Crum CP, et al. ZYC101a for treatment of high-grade cervical intraepithelial neoplasia: a randomized controlled trial. Obstet Gynecol 2004; 103(2):317-26.
  29. Wu F, Long J, Wang S, Xing J, Li M, Zheng C. Live cell imaging fails to support viral-protein-mediated intercellular trafficking. Arch Virol 2012; 157(7):1383-6.
  30. Li ML, Guo H, Ding Q, Zheng CF. A multiple functional protein: the herpes simplex virus type 1 tegument protein VP22. Virol Sinica 2009; 24(3):153-61.
  31. Kim TW, Hung CF, Kim JW, Juang J, Chen PJ, He L, et al. Vaccination with a DNA vaccine encoding herpes simplex virus type 1 VP22 linked to antigen generates long-term antigen-specific CD8-positive memory T cells and protective immunity. Hum Gene Ther 2004; 15(2):167-77.
  32. Michel N, Osen W, Gissmann L, Schumacher TN, Zentgraf H, Müller M. Enhanced immunogenicity of HPV 16 E7 fusion proteins in DNA vaccination. Virology 2002; 294(1):47-59.
  33. Trimble CL, Peng S, Kos F, Gravitt P, Viscidi R, Sugar E, et al. A phase I trial of a human papillomavirus DNA vaccine for HPV16+ cervical intraepithelial neoplasia 2/3. Clin Cancer Res 2009; 15(1):361-7.
  34. Beerens A, Rots M, Vries EF, Haisma HJ. Fusion of herpes simplex virus thymidine kinase to VP22 does not result in intercellular trafficking of the protein. Int J Mol Med 2007; 19(5):841-9.
  35. Wang S. 195. Tat peptide conjugates of low molecular weight polyethylenimine as effective non-viral gene delivery vectors. Mol Ther 2006; 2:13.
  36. Gan L, Jia R, Zhou L, Guo J, Fan M. Fusion of CTLA-4 with HPV16 E7 and E6 enhanced the potency of therapeutic HPV DNA vaccine. PloS One 2014; 9(9):e108892.
  37. Morrow MP, Kraynyak KA, Sylvester AJ, Shen X, Amante D, Sakata L, et al. Augmentation of cellular and humoral immune responses to HPV16 and HPV18 E6 and E7 antigens by VGX-3100. Mol Ther Oncolytics 2016; 3:16025.
  38. Joffre OP, Segura E, Savina A, Amigorena S. Cross-presentation by dendritic cells. Nat Rev Immunol 2012; 12(8):557-69.
  39. Kallen KJ, Heidenreich R, Schnee M, Petsch B, Schlake T, Thess A, et al. A novel, disruptive vaccination technology: self-adjuvanted RNActive® vaccines. Hum Vaccines Immunother 2013; 9(10):2263-76.
  40. Kim TJ, Jin HT, Hur SY, Yang HG, Seo YB, Hong SR, et al. Clearance of persistent HPV infection and cervical lesion by therapeutic DNA vaccine in CIN3 patients. Nat Commun 2014; 5:5317.
  41. Bagarazzi ML, Yan J, Morrow MP, Shen X, Parker RL, Lee JC, et al. Immunotherapy against HPV16/18 generates potent TH1 and cytotoxic cellular immune responses. Sci Transl Med 2012; 4(155):155ra38.
  42. Yang A, Jeang J, Cheng K, Cheng T, Yang B, Wu TC, et al. Current state in the development of candidate therapeutic HPV vaccines. Expert Rev Vaccines 2016; 15(8):989-1007.