Skip to main content
SpringerLink
Log in

Electroporation Based TriGrid™ Delivery System (TDS) for DNA Vaccine Administration

  • Chapter
  • First Online:
Gene Vaccines

  • 1383 Accesses

Abstract

Electroporation (EP) is a promising device based method for increasing the delivery of genetic vaccines to their intracellular site of action. This is achieved through the brief application of electrical fields at the target tissue site in the presence of the vaccine candidate. Non-clinical studies comparing EP mediated delivery with conventional injection methods have demonstrated 10–1,000 fold increases in antigen expression and subsequent cellular and humoral immune responses. Prompted by this promising data, multiple groups have developed EP device technologies to support translation of this delivery modality into the clinical setting. Among these is the TriGridTM Delivery System (TDS) platform developed by Ichor Medical Systems. TDS devices are characterized by the integration of the means for agent administration and EP application into a single automated device which controls the site, rate, and timing of agent administration relative to the application of EP. This design ensures co-localization of the electrical fields with the site of genetic vaccine distribution and facilitates consistent procedure application independent of operator skill or experience. Device configurations for genetic vaccine delivery into either skeletal muscle or skin have been developed and are being evaluated in both non-clinical and clinical studies for delivery of a wide range of vaccine applications.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Aihara H, Miyazaki J (1998) Gene transfer into muscle by electroporation in vivo. Nat Biotechnol 16(9):867–870

    Article  PubMed  CAS  Google Scholar 

  • 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 (2010) Universal influenza DNA vaccine encoding conserved CD4+ T cell epitopes ­protects against lethal viral challenge in HLA-DR transgenic mice. Vaccine 28(3):664–672

    Article  PubMed  CAS  Google Scholar 

  • ASM-International (2009) Materials and coatings for medical devices: cardiovascular. Materials and Processes for Medical Devices, ASM International

    Google Scholar 

  • 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(27–28):3399–3408

    Article  PubMed  CAS  Google Scholar 

  • Babiuk S, Baca-Estrada ME, Foldvari M, Baizer L, Stout R, Storms M, Rabussay D, Widera G, Babiuk L (2003) Needle-free topical electroporation improves gene expression from plasmids administered in porcine skin. Mol Ther 8(6):992–998

    Article  PubMed  CAS  Google Scholar 

  • Babiuk S, Tsang C, van Drunen Littel-van den Hurk S, Babiuk LA, Griebel PJ (2007) A single HBsAg DNA vaccination in combination with electroporation elicits long-term antibody responses in sheep. Bioelectrochemistry 70(2):269–274

    Article  PubMed  CAS  Google Scholar 

  • 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(40):5450–5459

    Article  PubMed  CAS  Google Scholar 

  • 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(36):13538–13543

    Article  PubMed  CAS  Google Scholar 

  • Cook IF, Williamson M, Pond D (2006) Definition of needle length required for intramuscular deltoid injection in elderly adults: an ultrasonographic study. Vaccine 24(7):937–940

    Article  PubMed  CAS  Google Scholar 

  • Crowley JM (1973) Electrical breakdown of bimolecular lipid membranes as an electromechanical instability. Biophys J 13(7):711–724

    Article  PubMed  CAS  Google Scholar 

  • Daley K (2000) Needlestick Prevention Bill unanimously passes Senate. Ohio Nurses Rev 75(3):7–8

    PubMed  CAS  Google Scholar 

  • Dolter KE, Evans CF, Ellefsen B, Song J, Boente-Carrera M, Vittorino R, Rosenberg TJ, Hannaman D, Vasan S (2011) Immunogenicity, safety, biodistribution and persistence of ADVAX, a ­prophylactic DNA vaccine for HIV-1, delivered by in vivo electroporation. Vaccine 29(4):795–803

    Article  PubMed  CAS  Google Scholar 

  • Donnelly J, Berry K, Ulmer JB (2003) Technical and regulatory hurdles for DNA vaccines. Int J Parasitol 33(5–6):457–467

    Article  PubMed  CAS  Google Scholar 

  • Drabick JJ, Glasspool-Malone J, King A, Malone RW (2001) Cutaneous transfection and immune responses to intradermal nucleic acid vaccination are significantly enhanced by in vivo electropermeabilization. Mol Ther 3(2):249–255

    Article  PubMed  CAS  Google Scholar 

  • Dupuis M, Denis-Mize K, Woo C, Goldbeck C, Selby MJ, Chen M, Otten GR, Ulmer JB, Donnelly JJ, Ott G, McDonald DM (2000) Distribution of DNA vaccines determines their immunogenicity after intramuscular injection in mice. J Immunol 165(5):2850–2858

    PubMed  CAS  Google Scholar 

  • Forte G, Petrucci F, Bocca B (2008) Metal allergens of growing significance: epidemiology, immunotoxicology, strategies for testing and prevention. Inflamm Allergy Drug Targets 7(3):145–162

    Article  PubMed  CAS  Google Scholar 

  • Gardiner DF, Huang Y, Basu S, Leung L, Song Y, Chen Z, Ho DD (2006) Multiple-site DNA vaccination enhances immune responses in mice. Vaccine 24(3):287–292

    Article  PubMed  CAS  Google Scholar 

  • 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(27):3598–3604

    Article  PubMed  CAS  Google Scholar 

  • Glasspool-Malone J, Somiari S, Drabick JJ, Malone RW (2000) Efficient nonviral cutaneous transfection. Mol Ther 2(2):140–146

    Article  PubMed  CAS  Google Scholar 

  • Greatbatch W (1981) Metal electrodes in bioengineering. Crit Rev Bioeng 5(1):1–36

    PubMed  CAS  Google Scholar 

  • Heller R, Jaroszeski M, Atkin A, Moradpour D, Gilbert R, Wands J, Nicolau C (1996) In vivo gene electroinjection and expression in rat liver. FEBS Lett 389(3):225–228

    Article  PubMed  CAS  Google Scholar 

  • Hsu JW, Matiz C, Jacob SE (2010) Nickel allergy: localized, Id, and systemic manifestations in children. Pediatr Dermatol

    Google Scholar 

  • 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(25):2779–2788

    Article  PubMed  CAS  Google Scholar 

  • Kang TH, Chung JY, Monie A, Pai SI, Hung CF, Wu TC (2010) Enhancing DNA vaccine potency by co-administration of xenogenic MHC class-I DNA. Gene Ther 17(4):531–540

    Article  PubMed  CAS  Google Scholar 

  • Khan AS, Smith LC, Abruzzese RV, Cummings KK, Pope MA, Brown PA, Draghia-Akli R (2003) Optimization of electroporation parameters for the intramuscular delivery of plasmids in pigs. DNA Cell Biol 22(12):807–814

    Article  PubMed  CAS  Google Scholar 

  • 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(6):e2517

    Article  PubMed  Google Scholar 

  • LeBlanc R, Vasquez Y, Hannaman D, Kumar N (2008) Markedly enhanced immunogenicity of a Pfs25 DNA-based malaria transmission-blocking vaccine by in vivo electroporation. Vaccine 26(2):185–192

    Article  PubMed  CAS  Google Scholar 

  • Liu L, Fang Q, Deng F, Wang H, Yi CE, Ba L, Yu W, Lin RD, Li T, Hu Z, Ho DD, Zhang L, Chen Z (2007) Natural mutations in the receptor binding domain of spike glycoprotein determine the reactivity of cross-neutralization between palm civet coronavirus and severe acute respiratory syndrome coronavirus. J Virol 81(9):4694–4700

    Article  PubMed  CAS  Google Scholar 

  • 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(4):1056–1061

    Article  PubMed  CAS  Google Scholar 

  • Luxembourg A, Hannaman D, Ellefsen B, Nakamura G, Bernard R (2006) Enhancement of immune responses to an HBV DNA vaccine by electroporation. Vaccine 24(21):4490–4493

    Article  PubMed  CAS  Google Scholar 

  • Luxembourg A, Evans CF, Hannaman D (2007) Electroporation-based DNA immunisation: translation to the clinic. Expert Opin Biol Ther 7(11):1647–1664

    Article  PubMed  CAS  Google Scholar 

  • Luxembourg A, Hannaman D, Nolan E, Ellefsen B, Nakamura G, Chau L, Tellez O, Little S, Bernard R (2008a) Potentiation of an anthrax DNA vaccine with electroporation. Vaccine 26(40):5216–5222

    Article  PubMed  CAS  Google Scholar 

  • Luxembourg A, Hannaman D, Wills K, Bernard R, Tennant BC, Menne S, Cote PJ (2008b) Immunogenicity in mice and rabbits of DNA vaccines expressing woodchuck hepatitis virus antigens. Vaccine 26(32):4025–4033

    Article  PubMed  CAS  Google Scholar 

  • Mathiesen I (1999) Electropermeabilization of skeletal muscle enhances gene transfer in vivo. Gene Ther 6(4):508–514

    Article  PubMed  CAS  Google Scholar 

  • 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(11):893–899

    Article  PubMed  CAS  Google Scholar 

  • Mir LM, Moller PH, Andre F, Gehl J (2005) Electric pulse-mediated gene delivery to various animal tissues. Adv Genet 54:83–114

    Article  PubMed  CAS  Google Scholar 

  • Mooney H (2009) E.U. laws to enforce needlestick safety. Nurs Times 105(22):1

    Google Scholar 

  • Nchinda G, Kuroiwa J, Oks M, Trumpfheller C, Park CG, Huang Y, Hannaman D, Schlesinger SJ, Mizenina O, Nussenzweig MC, Uberla K, Steinman RM (2008) The efficacy of DNA vaccination is enhanced in mice by targeting the encoded protein to dendritic cells. J Clin Invest 118(4):1427–1436

    Article  PubMed  CAS  Google Scholar 

  • NCT00471133 (2009) Safety and immunogenicity of a melanoma DNA vaccine delivered by electroporation. http://clinicaltrials.gov/ct2/show/NCT00471133. Accessed 30 Nov., 2009

  • NCT00545987 (2009) Study of a potential preventive vaccine against HIV in healthy volunteers (ADVAX-EP). http://clinicaltrials.gov/ct2/show/NCT00545987. Accessed 27 Nov., 2009

  • NCT01138410 (2010) Study of a DNA immunotherapy to treat melanoma. http://clinicaltrials.gov/ct2/show/NCT01138410. Accessed 30 Nov., 2010

  • NCT01169077 (2010) EP1300 polyepitope DNA vaccine against Plasmodium falciparummalaria. http://clinicaltrials.gov/ct2/show/NCT01169077. Accessed 30 Nov., 2010

  • Nishi T, Yoshizato K, Yamashiro S, Takeshima H, Sato K, Hamada K, Kitamura I, Yoshimura T, Saya H, Kuratsu J, Ushio Y (1996) High-efficiency in vivo gene transfer using intraarterial plasmid DNA injection following in vivo electroporation. Cancer Res 56(5):1050–1055

    PubMed  CAS  Google Scholar 

  • Nomura M, Nakata Y, Inoue T, Uzawa A, Itamura S, Nerome K, Akashi M, Suzuki G (1996) In vivo induction of cytotoxic T lymphocytes specific for a single epitope introduced into an unrelated molecule. J Immunol Methods 193(1):41–49

    Article  PubMed  CAS  Google Scholar 

  • Ohlschlager P, Spies E, Alvarez G, Quetting M, Groettrup M (2010) The combination of TLR-9 adjuvantation and electroporation-mediated delivery enhances in vivo antitumor responses after vaccination with HPV-16 E7 encoding DNA. Int J Cancer 128(2):473–481

    Article  PubMed  Google Scholar 

  • Okino M, Mohri H (1987) Effects of a high-voltage electrical impulse and an anticancer drug on in vivo growing tumors. Jpn J Cancer Res 78(12):1319–1321

    PubMed  CAS  Google Scholar 

  • Otten G, Schaefer M, Doe B, Liu H, Srivastava I, Otten G, Schaefer M, Doe B, Liu H, Srivastava I, zur Megede J, O’Hagan D, Donnelly J, Widera G, Rabussay D, Lewis MG, Barnett S, Ulmer JB (2004) Enhancement of DNA vaccine potency in rhesus macaques by electroporation. Vaccine 22(19):2489–2493

    Article  PubMed  CAS  Google Scholar 

  • Poland GA, Borrud A, Jacobson RM, McDermott K, Wollan PC, Brakke D, Charboneau JW (1997) Determination of deltoid fat pad thickness. Implications for needle length in adult immunization. JAMA 277(21):1709–1711

    Article  PubMed  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Schaldach M, Hubmann M, Hardt R, Weikl A (1989) Titanium nitride cardiac pacemaker electrodes. Biomed Tech (Berl) 34(7–8):185–190

    Article  CAS  Google Scholar 

  • Schaldach M, Hubmann M, Weikl A, Hardt R (1990) Sputter-deposited TiN electrode coatings for superior sensing and pacing performance. Pacing Clin Electrophysiol 13(12 Pt 2):1891–1895

    Article  PubMed  CAS  Google Scholar 

  • Selby M, Goldbeck C, Pertile T, Walsh R, Ulmer J (2000) Enhancement of DNA vaccine potency by electroporation in vivo. J Biotechnol 83(1–2):147–152

    Article  PubMed  CAS  Google Scholar 

  • Somiari S, Glasspool-Malone J, Drabick JJ, Gilbert RA, Heller R, Jaroszeski MJ, Malone RW (2000) Theory and in vivo application of electroporative gene delivery. Mol Ther 2(3):178–187

    Article  PubMed  CAS  Google Scholar 

  • Tenbusch M, Grunwald T, Niezold T, Storcksdieck Genannt Bonsmann M, Hannaman D, Norley S, Uberla K (2010) Codon-optimization of the hemagglutinin gene from the novel swine origin H1N1 influenza virus has differential effects on CD4(+) T-cell responses and immune effector mechanisms following DNA electroporation in mice. Vaccine 28(19):3273–3277

    Article  PubMed  CAS  Google Scholar 

  • Titomirov AV, Sukharev S, Kistanova E (1991) In vivo electroporation and stable transformation of skin cells of newborn mice by plasmid DNA. Biochim Biophys Acta 1088(1):131–134

    Article  PubMed  CAS  Google Scholar 

  • Tjelle TE, Rabussay D, Ottensmeier C, Mathiesen I, Kjeken R (2008) Taking electroporation-based delivery of DNA vaccination into humans: a generic clinical protocol. Methods Mol Biol 423:497–507

    Article  PubMed  CAS  Google Scholar 

  • Ulmer JB, Wahren B, Liu MA (2006) Gene-based vaccines: recent technical and clinical advances. Trends Mol Med 12(5):216–222

    Article  PubMed  CAS  Google Scholar 

  • van Drunen Littel-van den Hurk S, Hannaman D (2010) Electroporation for DNA immunization: clinical application. Expert Rev Vaccines 9(5):503–517

    Article  PubMed  CAS  Google Scholar 

  • van Drunen Littel-van den Hurk S, Babiuk SL, Babiuk LA (2004) Strategies for improved formulation and delivery of DNA vaccines to veterinary target species. Immunol Rev 199:113–125

    Article  PubMed  CAS  Google Scholar 

  • van Drunen Littel-van den Hurk S, Luxembourg A, Ellefsen B, Wilson D, Ubach A, Hannaman D, van den Hurk JV (2008) Electroporation-based DNA transfer enhances gene expression and immune responses to DNA vaccines in cattle. Vaccine 26(43):5503–5509

    Article  PubMed  CAS  Google Scholar 

  • 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(39):6445–6454

    Article  PubMed  CAS  Google Scholar 

  • 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. In vivo electroporation enhances the immunogenicity of an HIV-1 DNA vaccine candidate in healthy volunteers. PLoS One 2011;6(5):e19252

    Google Scholar 

  • 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(9):4635–4640

    PubMed  CAS  Google Scholar 

  • Wong TW, Chen CH, Huang CC, Lin CD, Hui SW (2006) Painless electroporation with a new needle-free microelectrode array to enhance transdermal drug delivery. J Control Release 110(3):557–565

    Article  PubMed  CAS  Google Scholar 

  • Yi CE, Ba L, Zhang L, Ho DD, Chen Z (2005) Single amino acid substitutions in the severe acute respiratory syndrome coronavirus spike glycoprotein determine viral entry and immunogenicity of a major neutralizing domain. J Virol 79(18):11638–11646

    Article  PubMed  CAS  Google Scholar 

  • Zimmermann U, Pilwat G, Holzapfel C, Rosenheck K (1976) Electrical hemolysis of human and bovine red blood cells. J Membr Biol 30(2):135–152

    PubMed  CAS  Google Scholar 

  • 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(24):11598–11607

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The author would like to thank the current and former colleagues at Ichor Medical Systems, Inc. who contributed to the work described herein including R. Bernard, B. Ellefsen, B. Bernard, S. Masterson, R. Betts, A. Ubach, G. Hague, C. Yih, C. Evans, K. Dolter, J. Song, and L. Chau. Work described herein was supported in part by a grant from the NIH SBIR program (GM064909).

Author information

Authors and Affiliations

  1. Ichor Medical Systems, Inc., San Diego, CA, USA

    Drew Hannaman

Authors
  1. Drew Hannaman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Drew Hannaman .

Editor information

Editors and Affiliations

  1. , Department of Molecular Biology, University of Salzburg, Hellbrunnerstrasse 34, Salzburg, 5020, Austria

    Josef Thalhamer

  2. , Department of Molecular Biology, University of Salzburg, Hellbrunnerstrasse 34, Salzburg, 5020, Austria

    Richard Weiss

  3. , Department of Molecular Biology, University of Salzburg, Hellbrunnerstrasse 34, Salzburg, 5020, Austria

    Sandra Scheiblhofer

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag/Wien

About this chapter

Cite this chapter

Hannaman, D. (2012). Electroporation Based TriGrid™ Delivery System (TDS) for DNA Vaccine Administration. In: Thalhamer, J., Weiss, R., Scheiblhofer, S. (eds) Gene Vaccines. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0439-2_8

Download citation

Publish with us

Policies and ethics

Search

Navigation