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RNA Vaccines pp 193-200 | Cite as

Enhanced Delivery of DNA or RNA Vaccines by Electroporation

  • Kate E. BroderickEmail author
  • Laurent M. Humeau
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1499)

Abstract

Nucleic acid vaccines are a next-generation branch of vaccines which offer major benefits over their conventional protein, bacteria, or viral-based counterparts. However, to be effective in large mammals and humans, an enhancing delivery technology is required. Electroporation is a physical technique which results in improved delivery of large molecules through the cell membrane. In the case of plasmid DNA and mRNA, electroporation enhances both the uptake and expression of the delivered nucleic acids. The muscle is an attractive tissue for nucleic acid vaccination in a clinical setting due to the accessibility and abundance of the target tissue. Historical clinical studies of electroporation in the muscle have demonstrated the procedure to be generally well tolerated in patients. Previous studies have determined that optimized electroporation parameters (such as electrical field intensity, pulse length, pulse width and drug product formulation) majorly impact the efficiency of nucleic acid delivery. We provide an overview of DNA/RNA vaccination in the muscle of mice. Our results suggest that the technique is safe and effective and is highly applicable to a research setting as well as scalable to larger animals and humans.

Keywords

Electroporation Muscle Plasmid DNA Mouse DNA vaccine RNA vaccine 

Notes

Acknowledgments

The authors would like to thank Janess Mendoza, Rachel Elward, and Lauren Gites for help with compiling the manuscript and the animal procedures. This work was supported by Inovio Pharmaceuticals (Plymouth Meeting, PA).

References

  1. 1.
    Widera G, Austin M, Rabussay D et al (2000) Increased DNA vaccine delivery and immunogenicity by electroporation in vivo. J Immunol 164:4635–4640CrossRefPubMedGoogle Scholar
  2. 2.
    Prud’homme GJ, Draghia-Akli R, Wang Q (2007) Plasmid-based gene therapy of diabetes mellitus. Gene Ther 14:553–564CrossRefPubMedGoogle Scholar
  3. 3.
    Otten G, Schaefer M, Doe B et al (2004) Enhancement of DNA vaccine potency in rhesus macaques by electroporation. Vaccine 22:2489–2493CrossRefPubMedGoogle Scholar
  4. 4.
    Mathiesen I (1999) Electropermeabilization of skeletal muscle enhances gene transfer in vivo. Gene Ther 6:508–514CrossRefPubMedGoogle Scholar
  5. 5.
    Bagarazzi ML, Yan J, Morrow MP et al (2012) Immunotherapy against HPV16/18 generates potent TH1 and cytotoxic cellular immune responses. Sci Transl Med 4:155ra138CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    El-Kamary SS, Billington M, Deitz S et al (2012) Safety and tolerability of the Easy Vax clinical epidermal electroporation system in healthy adults. Mol Ther 20:214–220CrossRefPubMedGoogle Scholar
  7. 7.
    Trimble CL, Morrow MP, Kraynyak KA et al (2015) Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3: a randomised, double-blind, placebo-controlled phase 2b trial. Lancet. doi: 10.1016/S0140-6736(15)00239-1 PubMedCentralGoogle Scholar
  8. 8.
    Cu Y, Broderick KE, Banerjee K et al (2013) Enhanced delivery and potency of self-amplifying mRNA vaccines by electroporation in situ. Vaccines (Basel) 1:367–383CrossRefGoogle Scholar
  9. 9.
    Andre S, Seed B, Eberle J et al (1998) Increased immune response elicited by DNA vaccination with a synthetic gp120 sequence with optimized codon usage. J Virol 72:1497–1503PubMedPubMedCentralGoogle Scholar
  10. 10.
    Deml L, Bojak A, Steck S et al (2001) Multiple effects of codon usage optimization on expression and immunogenicity of DNA candidate vaccines encoding the human immunodeficiency virus type 1 Gag protein. J Virol 75:10991–11001CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Muthumani K, Zhang D, Dayes NS et al (2003) Novel engineered HIV-1 East African Clade-A gp160 plasmid construct induces strong humoral and cell-mediated immune responses in vivo. Virology 314:134–146CrossRefPubMedGoogle Scholar
  12. 12.
    Schneider R, Campbell M, Nasioulas G et al (1997) Inactivation of the human immunodeficiency virus type 1 inhibitory elements allows Rev-independent expression of Gag and Gag/protease and particle formation. J Virol 71:4892–4903PubMedPubMedCentralGoogle Scholar
  13. 13.
    Yang JS, Kim JJ, Hwang D et al (2001) Induction of potent Th1-type immune responses from a novel DNA vaccine for West Nile virus New York isolate (WNV-NY1999). J Infect Dis 184:809–816CrossRefPubMedGoogle Scholar
  14. 14.
    Miyazaki S, Miyazaki J (2008) In vivo DNA electrotransfer into muscle. Dev Growth Differ 50(6):479–483CrossRefPubMedGoogle Scholar
  15. 15.
    Draghia-Akli R, Khan AS, Cummings KK et al (2002) Electrical enhancement of formulated plasmid delivery in animals. Technol Cancer Res Treat 1:365–372CrossRefPubMedGoogle Scholar
  16. 16.
    Atkins GJ, Fleeton MN, Sheahan BJ (2008) Therapeutic and prophylactic applications of alphavirus vectors. Expert Rev Mol Med 10:e33CrossRefPubMedGoogle Scholar
  17. 17.
    Barnett SW, Burke B, Sun Y et al (2010) Antibody-mediated protection against mucosal simian-human immunodeficiency virus challenge of macaques immunized with alphavirus replicon particles and boosted with trimeric envelope glycoprotein in MF59 adjuvant. J Virol 84:5975–5985CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Robert-Guroff M (2007) Replicating and non-replicating viral vectors for vaccine development. Curr Opin Biotechnol 18:546–556CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Smerdou C, Liljestrom P (1999) Non-viral amplification systems for gene transfer: vectors based on alphaviruses. Curr Opin Mol Ther 1:244–251PubMedGoogle Scholar
  20. 20.
    Zimmer G (2010) RNA replicons - a new approach for influenza virus immunoprophylaxis. Viruses 2:413–434CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Rayner JO, Dryga SA, Kamrud KI (2002) Alphavirus vectors and vaccination. Rev Med Virol 12:279–296CrossRefPubMedGoogle Scholar
  22. 22.
    Gronevik E, von Steyern FV, Kalhovde JM et al (2005) Gene expression and immune response kinetics using electroporation-mediated DNA delivery to muscle. J Gene Med 7:218–227CrossRefPubMedGoogle Scholar
  23. 23.
    Lin F, Shen X, McCoy JR et al (2011) A novel prototype device for electroporation-enhanced DNA vaccine delivery simultaneously to both skin and muscle. Vaccine 29:6771–6780CrossRefPubMedGoogle Scholar
  24. 24.
    Sardesai NY, Weiner DB (2011) Electroporation delivery of DNA vaccines: prospects for success. Curr Opin Immunol 23:421–429CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Diehl MC, Lee JC, Daniels SE et al (2013) Tolerability of intramuscular and intradermal delivery by CELLECTRA® adaptive constant current electroporation device in healthy volunteers. Hum Vaccin Immunother 9:2246–2252CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Inovio PharmaceuticalsPlymouth MeetingUSA

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