Application of Archaeosome Nanoparticles as a DNA Vaccine Delivery System and Evaluation of its Effect in a C57BL/6 Tumor Model

Authors
H. Karimi 1
H. Soleimanjahi 1
A. Abdoli 2
M. Shirmohammadi 1
A. Abdoli 2
1 Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
2 Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran
Abstract
Objective: More than 99% of cervical cancers contain human papillomavirus (HPV), particularly the high-risk HPV type 16 (HPV-16). Among therapeutic HPV vaccines, DNA vaccines have emerged as a potentially promising approach. The main problem with DNA vaccination is the efficient delivery of the genes. A different delivery system has been used to bypass this problem. Archaeosomes have shown high stability during oxidative stress. In this study, we prepared the archaeosome Halobacterium salinarum polar lipid and used it as a delivery system and adjuvants for formulation with the E6/E7/L1 chimeric plasmid as an HPV vaccine candidate.
Methods: The recombinant pIRES2-plasmid that contained an E6/E7/L1 chimeric gene of HPV were purified after extraction. Halobacterium salinarum total polar lipids were prepared according to a method by Bligh and Dyer. The archaeosome-pDNA complex was prepared by the addition of plasmid DNA to an archaeal lipid solution and the mixture kept at room temperature to allow for complex formation. Particle sizes and zeta potential of the samples were measured using dynamic light scattering. We measured the relative tumor volume after administration of TC-1 cells to C57BL/6 mice.
Results: Zeta potential of the anionic archaeosomes was -6.84mV while archaeosome-pDNA complexes were -29 mV. The highly negative zeta potential of archaeosome-pDNA complexes demonstrated excellent loading of the plasmid on the nanoparticle surface and electrostatic stability. The results showed that the archaeosome-containing E6/E7/L1 chimeric gene significantly inhibited the rate of tumor growth in comparison with the control groups.
Conclusion: Archaeosomes are easy and cost-economic to prepare and highly stable. They may hold tremendous promise as vaccine delivery vehicles

Keywords

[1]  Syrjänen KJ, Syrjänen SM. Papillomavirus infections in human pathology. Wiley, 2000; p: 21-31.
[2]  Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Muñoz N. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999; 189(1): 12-9.
[3]  Doorbar J. Papillomavirus life cycle organization and biomarker selection. Dis Markers 2007; 23(4): 297-313.
[4]  Chow LT, Broker TR. Human papillomavirus transcription. In: The papillomaviruses. Edited by Garcea RL, DiMaio D. Springer, 2007; 109-44.
[5]  Woodman CB, Collins SI, Young LS. The natural history of cervical HPV infection: unresolved issues. Nat Rev Cancer 2007; 7(1): 11-22.
[6]  WHO. IARC monographs on the evaluation of carcinogenic risks to humans. Volume 64, Human papillomaviruses. IARC, Lyon, France, 1995. Available from:
http://monographs.iarc.fr/ENG/Monographs/vol64/index.php
[7]  Muñoz N, Bosch FX, de Sanjosé S, Herrero R, Castellsagué X, Shah KV, Snijders PJ, Meijer CJ; International Agency for Research on Cancer Multicenter Cervical Cancer Study Group. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 2003; 348(6): 518-27.
[8]  Patel T, Morrison LK, Rady P, Tyring S. Epidermodysplasia verruciformis and susceptibility to HPV. Dis Markers 2010; 29(3-4): 199-206.
[9]  Castellsagué X. Natural history and epidemiology of HPV infection and cervical cancer. Gynecol Oncol 2008; 110(3 Suppl 2): S4-7.
[10]   Burd EM. Human papillomavirus and cervical cancer. Clin Microbiol Rev 2003; 16(1): 1-17.
[11]   Stanley M. Immunobiology of HPV and HPV vaccines. Gynecol Oncol 2008; 109(2 Suppl): S15-21.
[12]   Kutzler MA, Weiner DB. DNA vaccines: ready for prime time? Nat Rev Genet 2008; 9(10): 776-88.
[13]   Garnett MC. Gene-delivery systems using cationic polymers. Crit Rev Ther Drug Carrier Syst 1999; 16(2): 147-207.
[14]   Schwendener RA. Liposomes as vaccine delivery systems: a review of the recent advances. Ther Adv Vaccines 2014; 2(6): 159-82.
[15]   Singh M. Vaccine Adjuvants and Delivery Systems. John Wiley & Sons; 2007; p: 263-89.
[16]   Moghimipour E, Kargar M, Handali S. Archaeosomes as means of nano-drug delivery. Reviews in Medical Microbiology 2014; 25(2): 40-5.
[17]   Sündermann A, Eggers LF, Schwudke D. Liquid Extraction: Bligh and Dyer. In: Encyclopedia of Lipidomics. Edited by Wenk MR. Springer Netherlands, 2016; p: 1-4.
[18]   Anderson RP, Voziyanova E, Voziyanov Y. Flp and Cre expressed from Flp–2A–Cre and Flp–IRES–Cre transcription units mediate the highest level of dual recombinase-mediated cassette exchange. Nucleic Acids Res 2012; 40(8): e62.
[19]   Attar A, Ogan A, Yucel S, Turan K. The potential of archaeosomes as carriers of pDNA into mammalian cells. Artif Cells Nanomed Biotechnol 2016; 44(2): 710-6.
[20]   Lin KY, Guarnieri FG, Staveley-O'Carroll KF, Levitsky HI, August JT, Pardoll DM, Wu TC. Treatment of established tumors with a novel vaccine that enhances major histocompatibility class II presentation of tumor antigen. Cancer Res 1996; 56(1): 21-6.
[21]   Cui Z, Han SJ, Huang L. Coating of mannan on LPD particles containing HPV E7 peptide significantly enhances immunity against HPV-positive tumor. Pharm Res 2004; 21(6): 1018-25.
[22]   Bellone S, El-Sahwi K, Cocco E, Casagrande F, Cargnelutti M, Palmieri M, Bignotti E, Romani C, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD. Human papillomavirus type 16 (HPV-16) virus-like particle L1-specific CD8+ cytotoxic T lymphocytes (CTLs) are equally effective as E7-specific CD8+ CTLs in killing autologous HPV-16-positive tumor cells in cervical cancer patients: implications for L1 dendritic cell-based therapeutic vaccines. J Virol 2009; 83(13): 6779-89.
[23]   Massa S, Franconi R, Brandi R, Muller A, Mett V, Yusibov V, Venuti A. Anti-cancer activity of plant-produced HPV16 E7 vaccine. Vaccine 2007; 25(16): 3018-21.
[24]   Liu W, Gao F, Zhao KN, Zhao W, Fernando GJ, Thomas R, Frazer IH. Codon modified human papillomavirus type 16 E7 DNA vaccine enhances cytotoxic T-lymphocyte induction and anti-tumour activity. Virology 2002; 301(1): 43-52.
[25]   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.
[26]   Lin CT, Tsai YC, He L, Calizo R, Chou HH, Chang TC, Soong YK, Hung CF, Lai CH. A DNA vaccine encoding a codon-optimized human papillomavirus type 16 E6 gene enhances CTL response and anti-tumor activity. J Biomed Sci 2006; 13(4): 481-8.
[27]   Mirshahabi H, Soleimanjahi H, Pourpak Z, Meshkat Z, Hassan ZM. Production of human papilloma virus type 16 e6 oncoprotein as a recombinant protein in eukaryotic cells. Iran J Cancer Prev 2012; 5(1): 16-20.
[28]   Kadish AS, Timmins P, Wang Y, Ho GY, Burk RD, Ketz J, He W, Romney SL, Johnson A, Angeletti R, Abadi M; Albert Einstein Cervix Dysplasia Clinical Consortium. Regression of cervical intraepithelial neoplasia and loss of human papillomavirus (HPV) infection is associated with cell-mediated immune responses to an HPV type 16 E7 peptide. Cancer Epidemiol Biomarkers Prev 2002; 11(5): 483-8.
[29]   Ohlschläger P, Pes M, Osen W, Dürst M, Schneider A, Gissmann L, Kaufmann AM. An improved rearranged Human Papillomavirus Type 16 E7 DNA vaccine candidate (HPV-16 E7SH) induces an E7 wildtype-specific T cell response. Vaccine 2006; 24(15): 2880-93.
[30]   Meshkat Z, Soleimanjahi H, Mahmoudi M, Hassan ZM, Mirshahabi H, Meshkat M, Kheirandish M. CTL responses to a DNA vaccine encoding E7 gene of human papillomavirus type 16 from an Iranian isolate. Iran J Immunol 2008; 5(2): 82-91.
[31]   Peng S, Hung CF, Trimble C, He L, Yeatermeyer J, Wu TC. Development of a DNA vaccine targeting HPV-16 oncoprotein E6. Cancer Research 2004; 64(7 Supplement): 326.
[32]   Kaufmann AM, Nieland J, Schinz M, Nonn M, Gabelsberger J, Meissner H, Müller RT, Jochmus I, Gissmann L, Schneider A, Dürst M. HPV16 L1E7 chimeric virus-like particles induce specific HLA-restricted T cells in humans after in vitro vaccination. Int J Cancer 2001; 92(2): 285-93.
[33]   Minko T, Pakunlu RI, Wang Y, Khandare JJ, Saad M. New generation of liposomal drugs for cancer. Anticancer Agents Med Chem 2006; 6(6): 537-52.
[34]   Krishnan L, Sprott GD. Archaesome vaccine adjuvants for cross-priming CD8+ T cell immunity. In: Vaccine adjuvants and delivery systems. Edited by Singh M. Hoboken, NJ: John Wiley & Sons, 2007; p: 263-94
[35]   Rethore G, Montier T, Le Gall T, Delepine P, Gammas-Marion S, Lemiegre L, Lehn P, Benvegnu T. Archaesomes based on synthetic tetraether-like lipids as novel versatile gene delivery systems. Chem Commun (Camb) 2007; 20: 2054-6.
Pathobiology Reserach
Volume 19, Issue 4
September 2017
Pages 71-85