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Current Drug Delivery

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ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

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Research Article

Immunogenicity and Biodistribution of Anthrax DNA Vaccine Delivered by Intradermal Electroporation

Author(s): Na Young Kim, Won Rak Son, Jun Young Choi, Chi Ho Yu, Gyeung Haeng Hur, Seong Tae Jeong, Young Kee Shin, Sung Youl Hong and Sungho Shin*

Volume 17, Issue 5, 2020

Page: [414 - 421] Pages: 8

DOI: 10.2174/1567201817666200414144550

Price: $65

Abstract

Purpose: Anthrax is a lethal bacterial disease caused by gram-positive bacterium Bacillus anthracis and vaccination is a desirable method to prevent anthrax infections. In the present study, DNA vaccine encoding a protective antigen of Bacillus anthracis was prepared and we investigated the influence of DNA electrotransfer in the skin on the induced immune response and biodistribution.

Methods and Results: The tdTomato reporter gene for the whole animal in vivo imaging was used to assess gene transfer efficiency into the skin as a function of electrical parameters. Compared to that with 25 V, the transgene expression of red fluorescent protein increased significantly when a voltage of 90 V was used. Delivery of DNA vaccines expressing Bacillus anthracis protective antigen domain 4 (PAD4) with an applied voltage of 90 V induced robust PA-D4-specific antibody responses. In addition, the in vivo fate of anthrax DNA vaccine was studied after intradermal administration into the mouse. DNA plasmids remained at the skin injection site for an appropriate period of time after immunization. Intradermal administration of DNA vaccine resulted in detection in various organs (viz., lung, heart, kidney, spleen, brain, and liver), although the levels were significantly reduced.

Conclusion: Our results offer important insights into how anthrax DNA vaccine delivery by intradermal electroporation affects the immune response and biodistribution of DNA vaccine. Therefore, it may provide valuable information for the development of effective DNA vaccines against anthrax infection.

Keywords: Anthrax, biodistribution, DNA vaccine, electroporation, immune response, skin delivery.

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[1]
Moayeri, M.; Leppla, S.H.; Vrentas, C.; Pomerantsev, A.P.; Liu, S. Anthrax Pathogenesis. Annu. Rev. Microbiol., 2015, 69, 185-208.
[http://dx.doi.org/10.1146/annurev-micro-091014-104523] [PMID: 26195305]
[2]
Guichard, A.; Nizet, V.; Bier, E. New insights into the biological effects of anthrax toxins: linking cellular to organismal responses. Microbes Infect., 2012, 14(2), 97-118.
[http://dx.doi.org/10.1016/j.micinf.2011.08.016] [PMID: 21930233]
[3]
Lowe, D.E.; Glomski, I.J. Cellular and physiological effects of anthrax exotoxin and its relevance to disease. Front. Cell. Infect. Microbiol., 2012, 2, 76.
[http://dx.doi.org/10.3389/fcimb.2012.00076] [PMID: 22919667]
[4]
Hobernik, D.; Bros, M. DNA vaccines: how far from clinical use. Int. J. Mol. Sci., 2018, 19(11), 3605.
[http://dx.doi.org/10.3390/ijms19113605] [PMID: 30445702]
[5]
Ingolotti, M.; Kawalekar, O.; Shedlock, D.J.; Muthumani, K.; Weiner, D.B. DNA vaccines for targeting bacterial infections. Expert Rev. Vaccines, 2010, 9(7), 747-763.
[http://dx.doi.org/10.1586/erv.10.57] [PMID: 20624048]
[6]
Williams, J.A.; Carnes, A.E.; Hodgson, C.P. Plasmid DNA vaccine vector design: impact on efficacy, safety and upstream production. Biotechnol. Adv., 2009, 27(4), 353-370.
[http://dx.doi.org/10.1016/j.biotechadv.2009.02.003] [PMID: 19233255]
[7]
Lee, J.; Arun Kumar, S.; Jhan, Y.Y.; Bishop, C.J. Engineering DNA vaccines against infectious diseases. Acta Biomater., 2018, 80, 31-47.
[http://dx.doi.org/10.1016/j.actbio.2018.08.033] [PMID: 30172933]
[8]
Suschak, J.J.; Williams, J.A.; Schmaljohn, C.S. Advancements in DNA vaccine vectors, non-mechanical delivery methods, and molecular adjuvants to increase immunogenicity. Hum. Vaccin. Immunother., 2017, 13(12), 2837-2848.
[http://dx.doi.org/10.1080/21645515.2017.1330236] [PMID: 28604157]
[9]
Saade, F.; Petrovsky, N. Technologies for enhanced efficacy of DNA vaccines. Expert Rev. Vaccines, 2012, 11(2), 189-209.
[http://dx.doi.org/10.1586/erv.11.188] [PMID: 22309668]
[10]
Okuda, K.; Wada, Y.; Shimada, M. Recent developments in preclinical DNA vaccination. Vaccines (Basel), 2014, 2(1), 89-106.
[http://dx.doi.org/10.3390/vaccines2010089] [PMID: 26344468]
[11]
Yarmush, M.L.; Golberg, A.; Serša, G.; Kotnik, T.; Miklavčič, D. Electroporation-based technologies for medicine: principles, applications, and challenges. Annu. Rev. Biomed. Eng., 2014, 16, 295-320.
[http://dx.doi.org/10.1146/annurev-bioeng-071813-104622] [PMID: 24905876]
[12]
Lambricht, L.; Lopes, A.; Kos, S.; Sersa, G.; Préat, V.; Vandermeulen, G. Clinical potential of electroporation for gene therapy and DNA vaccine delivery. Expert Opin. Drug Deliv., 2016, 13(2), 295-310.
[http://dx.doi.org/10.1517/17425247.2016.1121990] [PMID: 26578324]
[13]
Kupper, T.S.; Fuhlbrigge, R.C. Immune surveillance in the skin: mechanisms and clinical consequences. Nat. Rev. Immunol., 2004, 4(3), 211-222.
[http://dx.doi.org/10.1038/nri1310] [PMID: 15039758]
[14]
Romani, N.; Thurnher, M.; Idoyaga, J.; Steinman, R.M.; Flacher, V. Targeting of antigens to skin dendritic cells: possibilities to enhance vaccine efficacy. Immunol. Cell Biol., 2010, 88(4), 424-430.
[http://dx.doi.org/10.1038/icb.2010.39] [PMID: 20368713]
[15]
Kim, Y.C.; Prausnitz, M.R. Enabling skin vaccination using new delivery technologies. Curr. Top. Microbiol. Immunol., 2012, 351, 77-112.
[http://dx.doi.org/10.1007/82_2011_123] [PMID: 21472533]
[16]
Kim, N.Y.; Chang, D.S.; Kim, Y.; Kim, C.H.; Hur, G.H.; Yang, J.M.; Shin, S. Enhanced immune response to DNA vaccine encoding Bacillus anthracis PA-D4 protects mice against anthrax spore challenge. PLoS One, 2015, 10(10) e0139671
[http://dx.doi.org/10.1371/journal.pone.0139671] [PMID: 26430894]
[17]
Lee, C.; Kim, J.; Shin, S.G.; Hwang, S. Absolute and relative QPCR quantification of plasmid copy number in Escherichia coli. J. Biotechnol., 2006, 123(3), 273-280.
[http://dx.doi.org/10.1016/j.jbiotec.2005.11.014] [PMID: 16388869]
[18]
Whelan, J.A.; Russell, N.B.; Whelan, M.A. A method for the absolute quantification of cDNA using real-time PCR. J. Immunol. Methods, 2003, 278(1-2), 261-269.
[http://dx.doi.org/10.1016/S0022-1759(03)00223-0] [PMID: 12957413]
[19]
Cervia, L.D.; Yuan, F. Current progress in electrotransfection as a nonviral method for gene delivery. Mol. Pharm., 2018, 15(9), 3617-3624.
[http://dx.doi.org/10.1021/acs.molpharmaceut.8b00207] [PMID: 29889538]
[20]
Roos, A.K.; Moreno, S.; Leder, C.; Pavlenko, M.; King, A.; Pisa, P. Enhancement of cellular immune response to a prostate cancer DNA vaccine by intradermal electroporation. Mol. Ther., 2006, 13(2), 320-327.
[http://dx.doi.org/10.1016/j.ymthe.2005.08.005] [PMID: 16185933]
[21]
Hutnick, N.A.; Myles, D.J.F.; Ferraro, B.; Lucke, C.; Lin, F.; Yan, J.; Broderick, K.E.; Khan, A.S.; Sardesai, N.Y.; Weiner, D.B. Intradermal DNA vaccination enhanced by low-current electroporation improves antigen expression and induces robust cellular and humoral immune responses. Hum. Gene Ther., 2012, 23(9), 943-950.
[http://dx.doi.org/10.1089/hum.2012.055] [PMID: 22650607]
[22]
Sardesai, N.Y.; Weiner, D.B. Electroporation delivery of DNA vaccines: prospects for success. Curr. Opin. Immunol., 2011, 23(3), 421-429.
[http://dx.doi.org/10.1016/j.coi.2011.03.008] [PMID: 21530212]
[23]
Molnar, M.J.; Gilbert, R.; Lu, Y.; Liu, A.B.; Guo, A.; Larochelle, N.; Orlopp, K.; Lochmuller, H.; Petrof, B.J.; Nalbantoglu, J.; Karpati, G. Factors influencing the efficacy, longevity, and safety of electroporation-assisted plasmid-based gene transfer into mouse muscles. Mol. Ther., 2004, 10(3), 447-455.
[http://dx.doi.org/10.1016/j.ymthe.2004.06.642] [PMID: 15336645]
[24]
Heller, L.C.; Jaroszeski, M.J.; Coppola, D.; McCray, A.N.; Hickey, J.; Heller, R. Optimization of cutaneous electrically mediated plasmid DNA delivery using novel electrode. Gene Ther., 2007, 14(3), 275-280.
[http://dx.doi.org/10.1038/sj.gt.3302867] [PMID: 16988718]
[25]
Lin, F.; Shen, X.; Kichaev, G.; Mendoza, J.M.; Yang, M.; Armendi, P.; Yan, J.; Kobinger, G.P.; Bello, A.; Khan, A.S.; Broderick, K.E.; Sardesai, N.Y. Optimization of electroporation-enhanced intradermal delivery of DNA vaccine using a minimally invasive surface device. Hum. Gene Ther. Methods, 2012, 23(3), 157-168.
[http://dx.doi.org/10.1089/hgtb.2011.209] [PMID: 22794496]
[26]
Ribeiro, S.; Mairhofer, J.; Madeira, C.; Diogo, M.M.; Lobato da Silva, C.; Monteiro, G.; Grabherr, R.; Cabral, J.M. Plasmid DNA size does affect nonviral gene delivery efficiency in stem cells. Cell. Reprogram., 2012, 14(2), 130-137.
[http://dx.doi.org/10.1089/cell.2011.0093] [PMID: 22339198]
[27]
Todorova, B.; Adam, L.; Culina, S.; Boisgard, R.; Martinon, F.; Cosma, A.; Ustav, M.; Kortulewski, T.; Le Grand, R.; Chapon, C. Electroporation as a vaccine delivery system and a natural adjuvant to intradermal administration of plasmid DNA in macaques. Sci. Rep., 2017, 7(1), 4122.
[http://dx.doi.org/10.1038/s41598-017-04547-2] [PMID: 28646234]
[28]
Fonteneau, J.F.; Kavanagh, D.G.; Lirvall, M.; Sanders, C.; Cover, T.L.; Bhardwaj, N.; Larsson, M. Characterization of the MHC class I cross-presentation pathway for cell-associated antigens by human dendritic cells. Blood, 2003, 102(13), 4448-4455.
[http://dx.doi.org/10.1182/blood-2003-06-1801] [PMID: 12933572]
[29]
Tregoning, J.S.; Kinnear, E. Using plasmids as DNA vaccines for infectious diseases. Microbiol. Spectr., 2014, 2(6), 1-16.
[http://dx.doi.org/10.1128/microbiolspec.PLAS-0028-2014] [PMID: 26104452]
[30]
Faurez, F.; Dory, D.; Le Moigne, V.; Gravier, R.; Jestin, A. Biosafety of DNA vaccines: New generation of DNA vectors and current knowledge on the fate of plasmids after injection. Vaccine, 2010, 28(23), 3888-3895.
[http://dx.doi.org/10.1016/j.vaccine.2010.03.040] [PMID: 20371391]
[31]
Levy, M.Y.; Barron, L.G.; Meyer, K.B.; Szoka, F.C., Jr Characterization of plasmid DNA transfer into mouse skeletal muscle: evaluation of uptake mechanism, expression and secretion of gene products into blood. Gene Ther., 1996, 3(3), 201-211.
[PMID: 8646550]

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