DNA Electroporation of Multi-agent Vaccines Conferring Protection Against Select Agent Challenge: TriGrid Delivery System

  • Andrea M. Keane-Myers
  • Matt Bell
  • Drew Hannaman
  • Mark Albrecht
Part of the Methods in Molecular Biology book series (MIMB, volume 1121)


Effective multi-agent/multivalent vaccines that confer protection against more than one disease are highly desirable to the patient and to health-care professionals. Electroporation of DNA vaccines, whereby tissues injected with DNA are subjected to localized electrical currents, is an ideal platform technology that achieves protective immune responses to multivalent vaccination. Here, we describe an electroporation-based immunization technique capable of administering a cocktail of DNA vaccinations in vivo. Immune response measurements, including protection from pathogen challenge and induction of antigen-specific antibody responses and cell-mediated immune responses, are also discussed.

Key words

Anthrax Plague DNA vaccine Recombinant protein vaccine Intramuscular introduction 


  1. 1.
    CDC (2000) Use of anthrax vaccine in the united states: recommendations of the advisory committee on immunization practices. MMWR 49:1–22Google Scholar
  2. 2.
    Feodorova VA, Corbel MJ (2009) Prospects for new plague vaccines. Expert Rev Vaccines 8:1721–1738PubMedCrossRefGoogle Scholar
  3. 3.
    Meyer KF, Foster LE (1948) Measurement of protective serum antibodies in human volunteers inoculated with plague prophylactics. Stanford Med Bull 6:75–79PubMedGoogle Scholar
  4. 4.
    Vidor E (2007) The nature and consequences of intra- and inter-vaccine interference. J Comp Pathol 137(Suppl 1):S62–66PubMedCrossRefGoogle Scholar
  5. 5.
    Johnston SA, Talaat AM, McGuire MJ (2002) Genetic immunization: what’s in a name? Arch Med Res 33:325–329PubMedCrossRefGoogle Scholar
  6. 6.
    Robinson HL, Ginsberg HS, Davis HL, Johnston SA, Liu MA (1997) The scientific future of DNA for immunization. Am Acad MicrobiolGoogle Scholar
  7. 7.
    Sardesai NY, Weiner DB (2011) Electroporation delivery of DNA vaccines: prospects for success. Curr Opin Immunol 23:421–429PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Donnelly J, Berry K, Ulmer JB (2003) Technical and regulatory hurdles for DNA vaccines. Int J Parasitol 33:457–467PubMedCrossRefGoogle Scholar
  9. 9.
    Luxembourg A, Evans CF, Hannaman D (2007) Electroporation-based DNA immunisation: translation to the clinic. Expert Opin Biol Ther 7:1647–1664PubMedCrossRefGoogle Scholar
  10. 10.
    Capone S, Zampaglione I, Vitelli A et al (2006) Modulation of the immune response induced by gene electrotransfer of a hepatitis c virus DNA vaccine in nonhuman primates. J Immunol 177:7462–7471PubMedGoogle Scholar
  11. 11.
    Dupuy LC, Richards MJ, Ellefsen B et al (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 18:707–716PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Luckay A, Sidhu MK, Kjeken R et al (2007) Effect of plasmid DNA vaccine design and in vivo electroporation on the resulting vaccine-specific immune responses in rhesus macaques. J Virol 81:5257–5269PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Luxembourg A, Hannaman D, Ellefsen B, Nakamura G, Bernard R (2006) Enhancement of immune responses to an hbv DNA vaccine by electroporation. Vaccine 24:4490–4493PubMedCrossRefGoogle Scholar
  14. 14.
    McCluskie MJ, Brazolot Millan CL, Gramzinski RA et al (1999) Route and method of delivery of DNA vaccine influence immune responses in mice and non-human primates. Mol Med 5:287–300PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Widera G, Austin M, Rabussay D et al (2000) Increased DNA vaccine delivery and immunogenicity by electroporation in vivo. J Immunol 164:4635–4640PubMedGoogle Scholar
  16. 16.
    Albrecht MT, Livingston BD, Pesce JT, Bell MG, Hannaman D, Keane-Myers AM (2012) Electroporation of a multivalent DNA vaccine cocktail elicits a protective immune response against anthrax and plague. Vaccine 30:4872–4883PubMedCrossRefGoogle Scholar
  17. 17.
    McMahon JM, Wells DJ (2004) Electroporation for gene transfer to skeletal muscles: current status. BioDrugs 18:155–165PubMedCrossRefGoogle Scholar
  18. 18.
    Yuan TF (2008) Vaccine submission with muscle electroporation. Vaccine 26:1805–1806PubMedCrossRefGoogle Scholar
  19. 19.
    Kutzler MA, Weiner DB (2008) DNA vaccines: ready for prime time? Nat Rev Genet 9:776–788PubMedCrossRefGoogle Scholar
  20. 20.
    Braun S (2008) Muscular gene transfer using nonviral vectors. Curr Gene Ther 8:391–405PubMedCrossRefGoogle Scholar
  21. 21.
    Albrecht MT, Li H, Williamson ED et al (2007) Human monoclonal antibodies against anthrax lethal factor and protective antigen act independently to protect against bacillus anthracis infection and enhance endogenous immunity to anthrax. Infect Immun 75:5425–5433PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Williams JA, Carnes AE, Hodgson CP (2009) Plasmid DNA vaccine vector design: impact on efficacy, safety and upstream production. Biotechnol Adv 27:353–370PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Marin M (2008) Folding at the rhythm of the rare codon beat. Biotechnol J 3:1047–1057PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Andrea M. Keane-Myers
    • 1
  • Matt Bell
    • 1
  • Drew Hannaman
    • 1
  • Mark Albrecht
    • 1
  1. 1.Ichor Medical Systems, Inc.San DiegoUSA

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