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Current Status of Electroporation Technologies for Vaccine Delivery

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Novel Immune Potentiators and Delivery Technologies for Next Generation Vaccines

Abstract

With the first demonstration in the early 1990s that plasmid DNA could be taken up by somatic cells in vivo, resulting in expression of genes encoded by the plasmid and controlled by mammalian promoters, the stage was set for the investigation of the range of compelling applications for endogenous expression of proteins in animals and humans [1]. The finding that simple injection of purified plasmid DNA into a target tissue could induce sustained endogenous production of proteins from the recipient’s own cells precipitated a flurry of research that was hoped would quickly lead to therapies for genetic, metabolic, and infectious diseases, as well as cancer. Unfortunately, while the past two decades have seen substantial progress in understanding the advantages and limitations of nucleic acid-based interventions for human disease as well as licensure of multiple veterinary products, there are currently no DNA-based products approved for human use. With well over 100 human clinical studies of DNA-based product candidates conducted to date, the overarching conclusion from these studies is that, for the vast majority of applications, conventional injection of plasmid DNA into tissues at clinically feasible dose levels is unable to produce consistent, biologically meaningful responses, especially when scaled up from rodent models into larger animal species (including humans) [2]. One key factor contributing to these results is the relatively low efficiency with which DNA crosses the cell membrane to reach its intracellular site of action [3]. To address this issue, many approaches for improving the intracellular uptake of DNA have been evaluated, with electroporation-mediated DNA delivery being one of the most promising. This chapter will discuss the utility of DNA vaccines, and the promise that electroporation delivery systems bring to the use of nucleic acid-based vaccine strategies, as well as the potential impact of electroporation on the field of vaccines in general.

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References

  1. Wolff JA, Malone RW, Williams P, Chong W, Acsadi G, Jani A, Felgner PL (1990) Direct gene transfer into mouse muscle in vivo. Science 247:1465–1468

    Article  PubMed  CAS  Google Scholar 

  2. Ulmer JB, Wahren B, Liu MA (2006) DNA vaccines: recent technological and clinical advances. Discov Med 6:109–112

    PubMed  Google Scholar 

  3. Donnelly J, Berry K, Ulmer JB (2003) Technical and regulatory hurdles for DNA vaccines. Int J Parasitol 33:457–467

    Article  PubMed  CAS  Google Scholar 

  4. Ingolotti M, Kawalekar O, Shedlock DJ, Muthumani K, Weiner DB (2010) DNA vaccines for targeting bacterial infections. Expert Rev Vaccines 9:747–763

    Article  PubMed  CAS  Google Scholar 

  5. Kutzler MA, Weiner DB (2008) DNA vaccines: ready for prime time? Nat Rev Genet 9:776–788

    Article  PubMed  CAS  Google Scholar 

  6. Buchbinder SP, Mehrotra DV, Duerr A, Fitzgerald DW, Mogg R, Li D, Gilbert PB, Lama JR, Marmor M, Del Rio C, McElrath MJ, Casimiro DR, Gottesdiener KM, Chodakewitz JA, Corey L, Robertson MN (2008) Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet 372:1881–1893

    Article  PubMed  CAS  Google Scholar 

  7. Nayak S, Herzog RW (2010) Progress and prospects: immune responses to viral vectors. Gene Ther 17:295–304

    Article  PubMed  CAS  Google Scholar 

  8. Mingozzi F, High KA (2011) Immune responses to AAV in clinical trials. Curr Gene Ther 11:321–330

    Article  PubMed  CAS  Google Scholar 

  9. Davis BS, Chang GJ, Cropp B, Roehrig JT, Martin DA, Mitchell CJ, Bowen R, Bunning ML (2001) West Nile virus recombinant DNA vaccine protects mouse and horse from virus challenge and expresses in vitro a noninfectious recombinant antigen that can be used in enzyme-linked immunosorbent assays. J Virol 75:4040–4047

    Article  PubMed  CAS  Google Scholar 

  10. Corbeil S, Kurath G, La Patra SE (2000) Fish DNA vaccine against infectious hematopoietic necrosis virus: efficacy of various routes of immunisation. Fish Shellfish Immunol 10:711–723

    Article  PubMed  CAS  Google Scholar 

  11. Bergman PJ, Camps-Palau MA, McKnight JA, Leibman NF, Craft DM, Leung C, Liao J, Riviere I, Sadelain M, Hohenhaus AE, Gregor P, Houghton AN, Perales MA, Wolchok JD (2006) Development of a xenogeneic DNA vaccine program for canine malignant melanoma at the Animal Medical Center. Vaccine 24:4582–4585

    Article  PubMed  CAS  Google Scholar 

  12. Liu MA (2011) DNA vaccines: an historical perspective and view to the future. Immunol Rev 239:62–84

    Article  PubMed  CAS  Google Scholar 

  13. Ferraro B, Morrow MP, Hutnick NA, Shin TH, Lucke CE, Weiner DB (2011) Clinical applications of DNA vaccines: current progress. Clin Infect Dis 53:296–302

    Article  PubMed  CAS  Google Scholar 

  14. Aihara H, Miyazaki J (1998) Gene transfer into muscle by electroporation in vivo. Nat Biotechnol 16:867–870

    Article  PubMed  CAS  Google Scholar 

  15. Mir LM, Bureau MF, Rangara R, Schwartz B, Scherman D (1998) Long-term, high level in vivo gene expression after electric pulse-mediated gene transfer into skeletal muscle. C R Acad Sci III 321:893–899

    Article  PubMed  CAS  Google Scholar 

  16. Mathiesen I (1999) Electropermeabilization of skeletal muscle enhances gene transfer in vivo. Gene Ther 6:508–514

    Article  PubMed  CAS  Google Scholar 

  17. Draghia-Akli R, Fiorotto ML, Hill LA, Malone PB, Deaver DR, Schwartz RJ (1999) Myogenic expression of an injectable protease-resistant growth hormone-releasing hormone augments long-term growth in pigs. Nat Biotechnol 17:1179–1183

    Article  PubMed  CAS  Google Scholar 

  18. Mir LM, Bureau MF, Gehl J, Rangara R, Rouy D, Caillaud JM, Delaere P, Branellec D, Schwartz B, Scherman D (1999) High-efficiency gene transfer into skeletal muscle mediated by electric pulses. Proc Natl Acad Sci USA 96:4262–4267

    Article  PubMed  CAS  Google Scholar 

  19. Widera G, Austin M, Rabussay D, Goldbeck C, Barnett SW, Chen M, Leung L, Otten GR, Thudium K, Selby MJ, Ulmer JB (2000) Increased DNA vaccine delivery and immunogenicity by electroporation in vivo. J Immunol 164:4635–4640

    PubMed  CAS  Google Scholar 

  20. Kadowaki S, Chen Z, Asanuma H, Aizawa C, Kurata T, Tamura S (2000) Protection against influenza virus infection in mice immunized by administration of hemagglutinin-expressing DNAs with electroporation. Vaccine 18:2779–2788

    Article  PubMed  CAS  Google Scholar 

  21. Selby M, Goldbeck C, Pertile T, Walsh R, Ulmer J (2000) Enhancement of DNA vaccine potency by electroporation in vivo. J Biotechnol 83:147–152

    Article  PubMed  CAS  Google Scholar 

  22. Zucchelli S, Capone S, Fattori E, Folgori A, Di Marco A, Casimiro D, Simon AJ, Laufer R, La Monica N, Cortese R, Nicosia A (2000) Enhancing B- and T-cell immune response to a hepatitis C virus E2 DNA vaccine by intramuscular electrical gene transfer. J Virol 74:11598–11607

    Article  PubMed  CAS  Google Scholar 

  23. Roos AK, Moreno S, Leder C, Pavlenko M, King A, Pisa P (2006) Enhancement of cellular immune response to a prostate cancer DNA vaccine by intradermal electroporation. Mol Ther 13:320–327

    Article  PubMed  CAS  Google Scholar 

  24. Hirao LA, Draghia-Akli R, Prigge JT, Yang M, Satishchandran A, Wu L, Hammarlund E, Khan AS, Babas T, Rhodes L, Silvera P, Slifka M, Sardesai NY, Weiner DB (2011) Multivalent smallpox DNA vaccine delivered by intradermal electroporation drives protective immunity in nonhuman primates against lethal monkeypox challenge. J Infect Dis 203:95–102

    Article  PubMed  CAS  Google Scholar 

  25. Martinon F, Kaldma K, Sikut R, Culina S, Romain G, Tuomela M, Adojaan M, Mannik A, Toots U, Kivisild T, Morin J, Brochard P, Delache B, Tripiciano A, Ensoli F, Stanescu I, Le Grand R, Ustav M (2009) Persistent immune responses induced by a human immunodeficiency virus DNA vaccine delivered in association with electroporation in the skin of nonhuman primates. Hum Gene Ther 20:1291–1307

    Article  PubMed  CAS  Google Scholar 

  26. Luxembourg A, Evans CF, Hannaman D (2007) Electroporation-based DNA immunisation: translation to the clinic. Expert Opin Biol Ther 7:1647–1664

    Article  PubMed  CAS  Google Scholar 

  27. Rabussay D (2008) Applicator and electrode design for in vivo DNA delivery by electroporation. Methods Mol Biol 423:35–59

    Article  PubMed  CAS  Google Scholar 

  28. Hannaman D (2011) Electroporation-based Trigridâ„¢ delivery system (TDS) for DNA vaccine administration. In: Thalhamer J, Weiss R, Scheiblhofer S (eds) Gene vaccines. Springer, New York (Chapter 8)

    Google Scholar 

  29. Wallace M, Evans B, Woods S, Mogg R, Zhang L, Finnefrock AC, Rabussay D, Fons M, Mallee J, Mehrotra D, Schodel F, Musey L (2009) Tolerability of two sequential electroporation treatments using MedPulser DNA delivery system (DDS) in healthy adults. Mol Ther 17:922–928

    Article  PubMed  CAS  Google Scholar 

  30. Tjelle TE, Salte R, Mathiesen I, Kjeken R (2006) A novel electroporation device for gene delivery in large animals and humans. Vaccine 24:4667–4670

    Article  PubMed  CAS  Google Scholar 

  31. Luxembourg A, Hannaman D, Ellefsen B, Nakamura G, Bernard R (2006) Enhancement of immune responses to an HBV DNA vaccine by electroporation. Vaccine 24:4490–4493

    Article  PubMed  CAS  Google Scholar 

  32. Draghia-Akli R, Khan AS, Brown PA, Pope MA, Wu L, Hirao L, Weiner DB (2008) Parameters for DNA vaccination using adaptive constant-current electroporation in mouse and pig models. Vaccine 26:5230–5237

    Article  PubMed  CAS  Google Scholar 

  33. Roos AK, Eriksson F, Walters DC, Pisa P, King AD (2009) Optimization of skin electroporation in mice to increase tolerability of DNA vaccine delivery to patients. Mol Ther 17:1637–1642

    Article  PubMed  CAS  Google Scholar 

  34. Broderick KE, Shen X, Soderholm J, Lin F, McCoy J, Khan AS, Yan J, Morrow MP, Patel A, Kobinger GP, Kemmerrer S, Weiner DB, Sardesai NY (2011) Prototype development and preclinical immunogenicity analysis of a novel minimally invasive electroporation device. Gene Ther 18:258–265

    Article  PubMed  CAS  Google Scholar 

  35. Donate A, Coppola D, Cruz Y, Heller R (2011) Evaluation of a novel non-penetrating electrode for use in DNA vaccination. PLoS One 6:e19181

    Article  PubMed  CAS  Google Scholar 

  36. Broderick KE, Kardos T, McCoy JR, Fons MP, Kemmerrer S, Sardesai NY (2011) Piezoelectric permeabilization of mammalian dermal tissue for in vivo DNA delivery leads to enhanced protein expression and increased immunogenicity. Hum Vaccin 7:22–28

    Article  PubMed  CAS  Google Scholar 

  37. Lin F, Shen X, McCoy JR, Mendoza JM, Yan J, Kemmerrer SV, Khan AS, Weiner DB, Broderick KE, Sardesai NY (2011) A novel prototype device for electroporation-enhanced DNA vaccine delivery simultaneously to both skin and muscle. Vaccine 29:6771–6780

    Article  PubMed  CAS  Google Scholar 

  38. Hooper JW, Ferro AM, Wahl-Jensen V (2008) Immune serum produced by DNA vaccination protects hamsters against lethal respiratory challenge with Andes virus. J Virol 82:1332–1338

    Article  PubMed  CAS  Google Scholar 

  39. Laddy DJ, Yan J, Kutzler M, Kobasa D, Kobinger GP, Khan AS, Greenhouse J, Sardesai NY, Draghia-Akli R, Weiner DB (2008) Heterosubtypic protection against pathogenic human and avian influenza viruses via in vivo electroporation of synthetic consensus DNA antigens. PLoS One 3:e2517

    Article  PubMed  CAS  Google Scholar 

  40. Liu KH, Ascenzi MA, Bellezza CA, Bezuidenhout AJ, Cote PJ, Gonzalez-Aseguinolaza G, Hannaman D, Luxembourg A, Evans CF, Tennant BC, Menne S (2011) Electroporation enhances immunogenicity of a DNA vaccine expressing woodchuck hepatitis virus surface antigen in woodchucks. J Virol 85:4853–4862

    Article  PubMed  CAS  Google Scholar 

  41. Peruzzi D, Mesiti G, Ciliberto G, La Monica N, Aurisicchio L (2010) Telomerase and HER-2/neu as targets of genetic cancer vaccines in dogs. Vaccine 28:1201–1208

    Article  PubMed  CAS  Google Scholar 

  42. Babiuk S, Baca-Estrada ME, Foldvari M, Storms M, Rabussay D, Widera G, Babiuk LA (2002) Electroporation improves the efficacy of DNA vaccines in large animals. Vaccine 20:3399–3408

    Article  PubMed  CAS  Google Scholar 

  43. Scheerlinck JP, Karlis J, Tjelle TE, Presidente PJ, Mathiesen I, Newton SE (2004) In vivo electroporation improves immune responses to DNA vaccination in sheep. Vaccine 22:1820–1825

    Article  PubMed  CAS  Google Scholar 

  44. Tollefsen S, Vordermeier M, Olsen I, Storset AK, Reitan LJ, Clifford D, Lowrie DB, Wiker HG, Huygen K, Hewinson G, Mathiesen I, Tjelle TE (2003) DNA injection in combination with electroporation: a novel method for vaccination of farmed ruminants. Scand J Immunol 57:229–238

    Article  PubMed  CAS  Google Scholar 

  45. Dupuy LC, Richards MJ, Ellefsen B, Chau L, Luxembourg A, Hannaman D, Livingston BD, Schmaljohn CS (2011) A DNA vaccine for Venezuelan equine encephalitis virus delivered by intramuscular electroporation elicits high levels of neutralizing antibodies in multiple animal models and provides protective immunity to mice and nonhuman primates. Clin Vaccine Immunol 18:707–716

    Article  PubMed  CAS  Google Scholar 

  46. Capone S, Zampaglione I, Vitelli A, Pezzanera M, Kierstead L, Burns J, Ruggeri L, Arcuri M, Cappelletti M, Meola A, Ercole BB, Tafi R, Santini C, Luzzago A, Fu TM, Colloca S, Ciliberto G, Cortese R, Nicosia A, Fattori E, Folgori A (2006) Modulation of the immune response induced by gene electrotransfer of a hepatitis C virus DNA vaccine in nonhuman primates. J Immunol 177:7462–7471

    PubMed  CAS  Google Scholar 

  47. Shan S, Jiang Y, Bu Z, Ellis T, Zeng X, Edwards J, Tian G, Li Y, Ge J, Chen H, Fenwick S (2011) Strategies for improving the efficacy of a H6 subtype avian influenza DNA vaccine in chickens. J Virol Methods 173:220–226

    Article  PubMed  CAS  Google Scholar 

  48. Jaini R, Hannaman D, Johnson JM, Bernard RM, Altuntas CZ, Delasalas MM, Kesaraju P, Luxembourg A, Evans CF, Tuohy VK (2006) Gene-based intramuscular interferon-beta therapy for experimental autoimmune encephalomyelitis. Mol Ther 14:416–422

    Article  PubMed  CAS  Google Scholar 

  49. Murakami T, Arai M, Sunada Y, Nakamura A (2006) VEGF 164 gene transfer by electroporation improves diabetic sensory neuropathy in mice. J Gene Med 8:773–781

    Article  PubMed  CAS  Google Scholar 

  50. Person R, Bodles-Brakhop AM, Pope MA, Brown PA, Khan AS, Draghia-Akli R (2008) Growth hormone-releasing hormone plasmid treatment by electroporation decreases offspring mortality over three pregnancies. Mol Ther 16:1891–1897

    Article  PubMed  CAS  Google Scholar 

  51. Tjelle TE, Corthay A, Lunde E, Sandlie I, Michaelsen TE, Mathiesen I, Bogen B (2004) Monoclonal antibodies produced by muscle after plasmid injection and electroporation. Mol Ther 9:328–336

    Article  PubMed  CAS  Google Scholar 

  52. Perez N, Bigey P, Scherman D, Danos O, Piechaczyk M, Pelegrin M (2004) Regulatable systemic production of monoclonal antibodies by in vivo muscle electroporation. Genet Vaccines Ther 2:2

    Article  PubMed  Google Scholar 

  53. Yamazaki T, Nagashima M, Ninomiya D, Arai Y, Teshima Y, Fujimoto A, Ainai A, Hasegawa H, Chiba J (2011) Passive immune-prophylaxis against influenza virus infection by the expression of neutralizing anti-hemagglutinin monoclonal antibodies from plasmids. Jpn J Infect Dis 64:40–49

    PubMed  CAS  Google Scholar 

  54. Allard B, Priam F, Deshayes F, Ducancel F, Boquet D, Wijkhuisen A, Couraud JY (2011) Electroporation-aided DNA immunization generates polyclonal antibodies against the native conformation of human endothelin B receptor. DNA Cell Biol 30:727–737

    Article  PubMed  CAS  Google Scholar 

  55. Alexandrenne C, Wijkhuisen A, Dkhissi F, Hanoux V, Creminon C, Boquet D, Couraud JY (2009) Generating antibodies against the native form of the human prion protein (hPrP) in wild-type animals: a comparison between DNA and protein immunizations. J Immunol Methods 341:41–49

    Article  PubMed  CAS  Google Scholar 

  56. Lucas ML, Heller L, Coppola D, Heller R (2002) IL-12 plasmid delivery by in vivo electroporation for the successful treatment of established subcutaneous B16.F10 melanoma. Mol Ther 5:668–675

    Article  PubMed  CAS  Google Scholar 

  57. Trochon-Joseph V, Martel-Renoir D, Mir LM, Thomaidis A, Opolon P, Connault E, Li H, Grenet C, Fauvel-Lafeve F, Soria J, Legrand C, Soria C, Perricaudet M, Lu H (2004) Evidence of antiangiogenic and antimetastatic activities of the recombinant disintegrin domain of metargidin. Cancer Res 64:2062–2069

    Article  PubMed  CAS  Google Scholar 

  58. Daud AI, DeConti RC, Andrews S, Urbas P, Riker AI, Sondak VK, Munster PN, Sullivan DM, Ugen KE, Messina JL, Heller R (2008) Phase I trial of interleukin-12 plasmid electroporation in patients with metastatic melanoma. J Clin Oncol 26:5896–5903

    Article  PubMed  CAS  Google Scholar 

  59. Chen MW, Cheng TJ, Huang Y, Jan JT, Ma SH, Yu AL, Wong CH, Ho DD (2008) A consensus-hemagglutinin-based DNA vaccine that protects mice against divergent H5N1 influenza viruses. Proc Natl Acad Sci USA 105:13538–13543

    Article  PubMed  CAS  Google Scholar 

  60. Price GE, Soboleski MR, Lo CY, Misplon JA, Pappas C, Houser KV, Tumpey TM, Epstein SL (2009) Vaccination focusing immunity on conserved antigens protects mice and ferrets against virulent H1N1 and H5N1 influenza A viruses. Vaccine 27:6512–6521

    Article  PubMed  CAS  Google Scholar 

  61. Alexander J, Bilsel P, del Guercio MF, Stewart S, Marinkovic-Petrovic A, Southwood S, Crimi C, Vang L, Walker L, Ishioka G, Chitnis V, Sette A, Assarsson E, Hannaman D, Botten J, Newman MJ (2009) Universal influenza DNA vaccine encoding conserved CD4+ T cell epitopes protects against lethal viral challenge in HLA-DR transgenic mice. Vaccine 28:664–672

    Article  PubMed  CAS  Google Scholar 

  62. Rosati M, Bergamaschi C, Valentin A, Kulkarni V, Jalah R, Alicea C, Patel V, von Gegerfelt AS, Montefiori DC, Venzon DJ, Khan AS, Draghia-Akli R, Van Rompay KK, Felber BK, Pavlakis GN (2009) DNA vaccination in rhesus macaques induces potent immune responses and decreases acute and chronic viremia after SIVmac251 challenge. Proc Natl Acad Sci USA 106:15831–15836

    Article  PubMed  CAS  Google Scholar 

  63. Belisle SE, Yin J, Shedlock DJ, Dai A, Yan J, Hirao L, Kutzler MA, Lewis MG, Andersen H, Lank SM, Karl JA, O’Connor DH, Khan A, Sardesai N, Chang J, Aicher L, Palermo RE, Weiner DB, Katze MG, Boyer J (2011) Long-term programming of antigen-specific immunity from gene expression signatures in the PBMC of rhesus macaques immunized with an SIV DNA vaccine. PLoS One 6:e19681

    Article  PubMed  CAS  Google Scholar 

  64. Yin J, Dai A, Lecureux J, Arango T, Kutzler MA, Yan J, Lewis MG, Khan A, Sardesai NY, Montefiore D, Ruprecht R, Weiner DB, Boyer JD (2011) High antibody and cellular responses induced to HIV-1 clade C envelope following DNA vaccines delivered by electroporation. Vaccine 29:6763–6770

    Article  PubMed  CAS  Google Scholar 

  65. Livingston BD, Little SF, Luxembourg A, Ellefsen B, Hannaman D (2010) Comparative performance of a licensed anthrax vaccine versus electroporation based delivery of a PA encoding DNA vaccine in rhesus macaques. Vaccine 28:1056–1061

    Article  PubMed  CAS  Google Scholar 

  66. Gardiner DF, Rosenberg T, Zaharatos J, Franco D, Ho DD (2009) A DNA vaccine targeting the receptor-binding domain of Clostridium difficile toxin A. Vaccine 27:3598–3604

    Article  PubMed  CAS  Google Scholar 

  67. Mallilankaraman K, Shedlock DJ, Bao H, Kawalekar OU, Fagone P, Ramanathan AA, Ferraro B, Stabenow J, Vijayachari P, Sundaram SG, Muruganandam N, Sarangan G, Srikanth P, Khan AS, Lewis MG, Kim JJ, Sardesai NY, Muthumani K, Weiner DB (2011) A DNA vaccine against chikungunya virus is protective in mice and induces neutralizing antibodies in mice and nonhuman primates. PLoS Negl Trop Dis 5:e928

    Article  PubMed  CAS  Google Scholar 

  68. Shedlock DJ, Talbott KT, Cress C, Ferraro B, Tuyishme S, Mallilankaraman K, Cisper NJ, Morrow MP, Wu SJ, Kawalekar OU, Khan AS, Sardesai NY, Muthumani K, Shen H, Weiner DB (2011) A highly optimized DNA vaccine confers complete protective immunity against high-dose lethal lymphocytic choriomeningitis virus challenge. Vaccine 29:6755–6762

    Article  PubMed  CAS  Google Scholar 

  69. van Drunen Littel-van den Hurk S, Lawman Z, Wilson D, Luxembourg A, Ellefsen B, van den Hurk JV, Hannaman D (2010) Electroporation enhances immune responses and protection induced by a bovine viral diarrhea virus DNA vaccine in newborn calves with maternal antibodies. Vaccine 28:6445–6454

    Article  PubMed  CAS  Google Scholar 

  70. Zhu Y, Lu F, Dai Y, Wang X, Tang J, Zhao S, Zhang C, Zhang H, Lu S, Wang S (2010) Synergistic enhancement of immunogenicity and protection in mice against Schistosoma japonicum with codon optimization and electroporation delivery of SjTPI DNA vaccines. Vaccine 28:5347–5355

    Article  PubMed  CAS  Google Scholar 

  71. Zhang X, Divangahi M, Ngai P, Santosuosso M, Millar J, Zganiacz A, Wang J, Bramson J, Xing Z (2007) Intramuscular immunization with a monogenic plasmid DNA tuberculosis vaccine: enhanced immunogenicity by electroporation and co-expression of GM-CSF transgene. Vaccine 25:1342–1352

    Article  PubMed  CAS  Google Scholar 

  72. Kim SA, Liang CM, Cheng IC, Cheng YC, Chiao MT, Tseng CJ, Lee F, Jong MH, Tao MH, Yang NS, Liang SM (2006) DNA vaccination against foot-and-mouth disease via electroporation: study of molecular approaches for enhancing VP1 antigenicity. J Gene Med 8:1182–1191

    Article  PubMed  CAS  Google Scholar 

  73. Saha S, Takeshita F, Sasaki S, Matsuda T, Tanaka T, Tozuka M, Takase K, Matsumoto T, Okuda K, Ishii N, Yamaguchi K, Klinman DM, Xin KQ, Okuda K (2006) Multivalent DNA vaccine protects mice against pulmonary infection caused by Pseudomonas aeruginosa. Vaccine 24:6240–6249

    Article  PubMed  CAS  Google Scholar 

  74. Wu CJ, Lee SC, Huang HW, Tao MH (2004) In vivo electroporation of skeletal muscles increases the efficacy of Japanese encephalitis virus DNA vaccine. Vaccine 22:1457–1464

    Article  PubMed  CAS  Google Scholar 

  75. Lladser A, Ljungberg K, Tufvesson H, Tazzari M, Roos AK, Quest AF, Kiessling R (2010) Intradermal DNA electroporation induces survivin-specific CTLs, suppresses angiogenesis and confers protection against mouse melanoma. Cancer Immunol Immunother 59:81–92

    Article  PubMed  CAS  Google Scholar 

  76. Berta GN, Mognetti B, Spadaro M, Trione E, Amici A, Forni G, Di Carlo F, Cavallo F (2005) Anti-HER-2 DNA vaccine protects Syrian hamsters against squamous cell carcinomas. Br J Cancer 93:1250–1256

    Article  PubMed  CAS  Google Scholar 

  77. Kalat M, Kupcu Z, Schuller S, Zalusky D, Zehetner M, Paster W, Schweighoffer T (2002) In vivo plasmid electroporation induces tumor antigen-specific CD8+ T-cell responses and delays tumor growth in a syngeneic mouse melanoma model. Cancer Res 62:5489–5494

    PubMed  CAS  Google Scholar 

  78. Porzia A, Lanzardo S, Citti A, Cavallo F, Forni G, Santoni A, Galandrini R, Paolini R (2010) Attenuation of PI3K/Akt-mediated tumorigenic signals through PTEN activation by DNA vaccine-induced anti-ErbB2 antibodies. J Immunol 184:4170–4177

    Article  PubMed  CAS  Google Scholar 

  79. Iurescia S, Fioretti D, Pierimarchi P, Signori E, Zonfrillo M, Tonon G, Fazio VM, Rinaldi M (2010) Genetic immunization with CDR3-based fusion vaccine confers protection and long-term tumor-free survival in a mouse model of lymphoma. J Biomed Biotechnol 2010:316069

    Article  PubMed  CAS  Google Scholar 

  80. Valentin A, von Gegerfelt A, Rosati M, Miteloudis G, Alicea C, Bergamaschi C, Jalah R, Patel V, Khan AS, Draghia-Akli R, Pavlakis GN, Felber BK (2010) Repeated DNA therapeutic vaccination of chronically SIV-infected macaques provides additional virological benefit. Vaccine 28:1962–1974

    Article  PubMed  CAS  Google Scholar 

  81. Peruzzi D, Gavazza A, Mesiti G, Lubas G, Scarselli E, Conforti A, Bendtsen C, Ciliberto G, La Monica N, Aurisicchio L (2010) A vaccine targeting telomerase enhances survival of dogs affected by B-cell lymphoma. Mol Ther 18:1559–1567

    Article  PubMed  CAS  Google Scholar 

  82. Best SR, Peng S, Juang CM, Hung CF, Hannaman D, Saunders JR, Wu TC, Pai SI (2009) Administration of HPV DNA vaccine via electroporation elicits the strongest CD8+ T cell immune responses compared to intramuscular injection and intradermal gene gun delivery. Vaccine 27:5450–5459

    Article  PubMed  CAS  Google Scholar 

  83. Patel V, Valentin A, Kulkarni V, Rosati M, Bergamaschi C, Jalah R, Alicea C, Minang JT, Trivett MT, Ohlen C, Zhao J, Robert-Guroff M, Khan AS, Draghia-Akli R, Felber BK, Pavlakis GN (2010) Long-lasting humoral and cellular immune responses and mucosal dissemination after intramuscular DNA immunization. Vaccine 28:4827–4836

    Article  PubMed  CAS  Google Scholar 

  84. Kraynyak KA, Kutzler MA, Cisper NJ, Khan AS, Draghia-Akli R, Sardesal NY, Lewis MG, Yan J, Weiner DB (2010) Systemic immunization with CCL27/CTACK modulates immune responses at mucosal sites in mice and macaques. Vaccine 28:1942–1951

    Article  PubMed  CAS  Google Scholar 

  85. Wells KE, Maule J, Kingston R, Foster K, McMahon J, Damien E, Poole A, Wells DJ (1997) Immune responses, not promoter inactivation, are responsible for decreased long-term expression following plasmid gene transfer into skeletal muscle. FEBS Lett 407:164–168

    Article  PubMed  CAS  Google Scholar 

  86. Gronevik E, von Steyern FV, Kalhovde JM, Tjelle TE, Mathiesen I (2005) Gene expression and immune response kinetics using electroporation-mediated DNA delivery to muscle. J Gene Med 7:218–227

    Article  PubMed  CAS  Google Scholar 

  87. Liu J, Kjeken R, Mathiesen I, Barouch DH (2008) Recruitment of antigen-presenting cells to the site of inoculation and augmentation of human immunodeficiency virus type 1 DNA vaccine immunogenicity by in vivo electroporation. J Virol 82:5643–5649

    Article  PubMed  CAS  Google Scholar 

  88. Durieux AC, Bonnefoy R, Busso T, Freyssenet D (2004) In vivo gene electrotransfer into skeletal muscle: effects of plasmid DNA on the occurrence and extent of muscle damage. J Gene Med 6:809–816

    Article  PubMed  CAS  Google Scholar 

  89. Ahlen G, Soderholm J, Tjelle T, Kjeken R, Frelin L, Hoglund U, Blomberg P, Fons M, Mathiesen I, Sallberg M (2007) In vivo electroporation enhances the immunogenicity of hepatitis C virus nonstructural 3/4A DNA by increased local DNA uptake, protein expression, inflammation, and infiltration of CD3+ T cells. J Immunol 179:4741–4753

    PubMed  CAS  Google Scholar 

  90. Dolter KE, Evans CF, Ellefsen B, Song J, Boente-Carrera M, Vittorino R, Rosenberg TJ, Hannaman D, Vasan S (2010) Immunogenicity, safety, biodistribution and persistence of ADVAX, a prophylactic DNA vaccine for HIV-1, delivered by in vivo electroporation. Vaccine 29:795–803

    Article  PubMed  CAS  Google Scholar 

  91. Brave A, Gudmundsdotter L, Sandstrom E, Haller BK, Hallengard D, Maltais AK, King AD, Stout RR, Blomberg P, Hoglund U, Hejdeman B, Biberfeld G, Wahren B (2010) Biodistribution, persistence and lack of integration of a multigene HIV vaccine delivered by needle-free ­intradermal injection and electroporation. Vaccine 28:8203–8209

    Article  PubMed  CAS  Google Scholar 

  92. Roos AK, Eriksson F, Timmons JA, Gerhardt J, Nyman U, Gudmundsdotter L, Brave A, Wahren B, Pisa P (2009) Skin electroporation: effects on transgene expression, DNA persistence and local tissue environment. PLoS One 4:e7226

    Article  PubMed  CAS  Google Scholar 

  93. Davis HL, Millan CL, Watkins SC (1997) Immune-mediated destruction of transfected muscle fibers after direct gene transfer with antigen-expressing plasmid DNA. Gene Ther 4:181–188

    Article  PubMed  CAS  Google Scholar 

  94. Guidance for Industry: Considerations for Plasmid DNA Vaccines for Infectious Disease Indications (November 2007) Food and Drug Administration Center for Biologics Evaluation and Research

    Google Scholar 

  95. Luckay A, Sidhu MK, Kjeken R, Megati S, Chong SY, Roopchand V, Garcia-Hand D, Abdullah R, Braun R, Montefiori DC, Rosati M, Felber BK, Pavlakis GN, Mathiesen I, Israel ZR, Eldridge JH, Egan MA (2007) Effect of plasmid DNA vaccine design and in vivo electroporation on the resulting vaccine-specific immune responses in rhesus macaques. J Virol 81:5257–5269

    Article  PubMed  CAS  Google Scholar 

  96. Wang Z, Troilo PJ, Wang X, Griffiths TG, Pacchione SJ, Barnum AB, Harper LB, Pauley CJ, Niu Z, Denisova L, Follmer TT, Rizzuto G, Ciliberto G, Fattori E, Monica NL, Manam S, Ledwith BJ (2004) Detection of integration of plasmid DNA into host genomic DNA following intramuscular injection and electroporation. Gene Ther 11:711–721

    Article  PubMed  CAS  Google Scholar 

  97. van Drunen Littel-van den Hurk S, Hannaman D (2010) Electroporation for DNA immunization: clinical application. Expert Rev Vaccines 9:503–517

    Article  PubMed  CAS  Google Scholar 

  98. Low L, Mander A, McCann K, Dearnaley D, Tjelle T, Mathiesen I, Stevenson F, Ottensmeier CH (2009) DNA vaccination with electroporation induces increased antibody responses in patients with prostate cancer. Hum Gene Ther 20:1269–1278

    Article  PubMed  CAS  Google Scholar 

  99. Stevenson FK, Mander A, Chudley L, Ottensmeier CH (2011) DNA fusion vaccines enter the clinic. Cancer Immunol Immunother 60:1147–1151

    Article  PubMed  CAS  Google Scholar 

  100. Sallberg M, Frelin L, Diepolder HM, Jung MC, Mathiesen I, Fons M, Ahlen G, Chen M, Weiland O (2010) Therapeutic DNA vaccination followed by standard-of-care therapy in patients with chronic hepatitis C: a rapid clearance of viremia. Mol Ther 18:S110

    Google Scholar 

  101. Vasan S, Hurley A, Schlesinger SJ, Hannaman D, Gardiner DF, Dugin DP, Boente-Carrera M, Vittorino R, Caskey M, Andersen J, Huang Y, Cox JH, Tarragona-Fiol T, Gill DK, Cheeseman H, Clark L, Dally L, Smith C, Schmidt C, Park HH, Kopycinski JT, Gilmour J, Fast P, Bernard R, Ho DD (2011) In vivo electroporation enhances the immunogenicity of an HIV-1 DNA vaccine candidate in healthy volunteers. PLoS One 6:e19252

    Article  PubMed  CAS  Google Scholar 

  102. Kopycinski J, Cheeseman H, Ashraf A, Gill D, Hayes P, Hannaman D, Gilmour J, Cox JH, Vasan S (2012) ADVAX DNA vaccine delivered via in vivo electroporation induced CD4 responses towards the alpha4beta7-binding V2 loop of HIV gp120 in healthy volunteers. Clin Vaccine Immunol 19:1557–1559

    Article  PubMed  CAS  Google Scholar 

  103. Yan J, Pankhong P, Shen X, Giffear M, Lee J, Harris D, Diaz D, Khan A, Bagarazzi M, Boyer J, Weiner DB, Sardesai NY (2010) Phase I safety and immunogenicity of HPV 16 and 18 DNA vaccines delivered via electroporation. Mol Ther 18:S184

    Article  CAS  Google Scholar 

  104. Yan J, Shen X, Giffear M, Lee J, Khan A, Harris D, Pankhong P, Shedlock D, Boyer J, Weiner DB, Bagarazzi M, Sardesai NY (2011) Induction of strong cellular and humoral immune responses following immunotherapy of post-LEEP CIN 2/3 with HPV 16 & 18 E6/E7 DNA vaccines. Mol Ther 19:S8

    Google Scholar 

  105. Pudney VA, Metheringham RL, Gunn B, Spendlove I, Ramage JM, Durrant LG (2010) DNA vaccination with T-cell epitopes encoded within Ab molecules induces high-avidity anti-tumor CD8+ T cells. Eur J Immunol 40:899–910

    Article  PubMed  CAS  Google Scholar 

  106. Inovio Pharmaceuticals (2010) Inovio Pharmaceuticals’ HIV DNA vaccine achieves strong T-cell immune responses in Phase I human trial. Press Release: November 17, 2010

    Google Scholar 

  107. Yang FQ, Yu YY, Wang GQ, Chen J, Li JH, Li YQ, Rao GR, Mo GY, Luo XR, Chen GM (2012) A pilot randomized controlled trial of dual-plasmid HBV DNA vaccine mediated by in vivo electroporation in chronic hepatitis B patients under lamivudine chemotherapy. J Viral Hepat 19:581–593

    Article  PubMed  Google Scholar 

  108. Jones S, Evans K, McElwaine-Johnn H, Sharpe M, Oxford J, Lambkin-Williams R, Mant T, Nolan A, Zambon M, Ellis J, Beadle J, Loudon PT (2009) DNA vaccination protects against an influenza challenge in a double-blind randomised placebo-controlled phase 1b clinical trial. Vaccine 27:2506–2512

    Article  PubMed  CAS  Google Scholar 

  109. Smith LR, Wloch MK, Ye M, Reyes LR, Boutsaboualoy S, Dunne CE, Chaplin JA, Rusalov D, Rolland AP, Fisher CL, Al-Ibrahim MS, Kabongo ML, Steigbigel R, Belshe RB, Kitt ER, Chu AH, Moss RB (2010) Phase 1 clinical trials of the safety and immunogenicity of adjuvanted plasmid DNA vaccines encoding influenza A virus H5 hemagglutinin. Vaccine 28:2565–2572

    Article  PubMed  CAS  Google Scholar 

  110. Spik KW, Badger C, Mathiessen I, Tjelle T, Hooper JW, Schmaljohn C (2008) Mixing of M segment DNA vaccines to Hantaan virus and Puumala virus reduces their immunogenicity in hamsters. Vaccine 26:5177–5181

    Article  PubMed  CAS  Google Scholar 

  111. Furuichi Y, Tokuyama H, Ueha S, Kurachi M, Moriyasu F, Kakimi K (2005) Depletion of CD25+CD4+T cells (Tregs) enhances the HBV-specific CD8+ T cell response primed by DNA immunization. World J Gastroenterol 11:3772–3777

    PubMed  Google Scholar 

  112. Gabrilovich DI, Nagaraj S (2009) Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 9:162–174

    Article  PubMed  CAS  Google Scholar 

  113. Menne S, Tennant BC, Gerin JL, Cote PJ (2007) Chemoimmunotherapy of chronic hepatitis B virus infection in the woodchuck model overcomes immunologic tolerance and restores T-cell responses to pre-S and S regions of the viral envelope protein. J Virol 81:10614–10624

    Article  PubMed  CAS  Google Scholar 

  114. Plotkin SA (2010) Correlates of protection induced by vaccination. Clin Vaccine Immunol 17:1055–1065

    Article  PubMed  CAS  Google Scholar 

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Evans, C.F., Hannaman, D. (2013). Current Status of Electroporation Technologies for Vaccine Delivery. In: Singh, M. (eds) Novel Immune Potentiators and Delivery Technologies for Next Generation Vaccines. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-5380-2_9

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