Skip to main content

Advertisement

SpringerLink
Log in

Electroporation for therapeutic DNA vaccination in patients

  • Review
  • Published:
Medical Microbiology and Immunology Aims and scope Submit manuscript

Abstract

DNA vaccination has historically failed to raise strong immune responses in humans. Recent delivery techniques such as the gene gun and in vivo electroporation (EP)/electrotransfer (ET) have completely changed the efficiency of DNA vaccines in humans. In vivo EP exerts multiple effects that contribute to its efficiency. The two central factors are most likely the increased DNA uptake due to the transient membrane destabilization, and the local tissue damage acting as an adjuvant. To date, several studies in humans have used in vivo EP/ET to deliver DNA. Some of these results have been quite promising with strong T cell responses and/or transient effects on the viral replication. This suggests that improved strategies of in vivo EP/ET can be a future way to deliver DNA in humans.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Ulmer JB et al (1993) Heterologous protection against influenza by injection of DNA encoding a viral protein. Science 259:1745–1749

    Article  CAS  PubMed  Google Scholar 

  2. Calarota S et al (1998) Cellular cytotoxic response induced by DNA vaccination in HIV-1-infected patients. Lancet 351(9112):1320–1325

    Article  CAS  PubMed  Google Scholar 

  3. MacGregor RR et al (1998) First human trial of a DNA-based vaccine for treatment of human immunodeficiency virus type 1 infection: safety and host response. J Infect Dis 178:92–100

    Article  CAS  PubMed  Google Scholar 

  4. Wang R et al (1998) Induction of antigen-specific cytotoxic T lymphocytes in humans by a malaria DNA vaccine. Science 282:476–480

    Article  CAS  PubMed  Google Scholar 

  5. Neumann E, Rosenheck K (1972) Permeability changes induced by electric impulses in vesicular membranes. J Membr Biol 10:279–290

    Article  CAS  PubMed  Google Scholar 

  6. Neumann E et al (1982) Gene transfer into mouse lyoma cells by electroporation in high electric fields. EMBO J 1:841–845

    CAS  PubMed Central  PubMed  Google Scholar 

  7. Mir LM et al (1991) Electrochemotherapy potentiation of antitumour effect of bleomycin by local electric pulses. Eur J Cancer 27:68–72

    Article  CAS  PubMed  Google Scholar 

  8. Belehradek M et al (1993) Electrochemotherapy, a new antitumor treatment. First clinical phase I-II trial. Cancer 72:3694–3700

    Article  CAS  PubMed  Google Scholar 

  9. Heller R (1995) Treatment of cutaneous nodules using electrochemotherapy. J Fla Med Assoc 82:147–150

    CAS  PubMed  Google Scholar 

  10. Heller R et al (1996) Phase I/II trial for the treatment of cutaneous and subcutaneous tumors using electrochemotherapy. Cancer 77:964–971

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  13. Ahlen G et al (2007) In vivo electroporation enhances the immunogenicity of hepatitis C virus nonstructural3/4A DNA by increased local DNA uptake, protein expression, inflammation, and infiltration of CD3+ cells. J Immunol 179:4741–4753

    Article  CAS  PubMed  Google Scholar 

  14. Luxembourg A et al (2006) Enhancement of immune responses to an HBV DNA vaccine by electroporation. Vaccine 24:4490–4493

    Article  CAS  PubMed  Google Scholar 

  15. Matzinger P (2002) The danger model: a renewed sense of self. Science 296:301–305

    Article  CAS  PubMed  Google Scholar 

  16. Schenten D, Medzhitov R (2011) The control of adaptive immune responses by the innate immune system. Adv Immunol 109:87–124

    Article  CAS  PubMed  Google Scholar 

  17. Bagarazzi ML (2012) Immunotherapy against HPV16/18 generates potent TH1 and cytotoxic cellular immune responses. Sci Transl Med 4:155ra138

    Article  PubMed  Google Scholar 

  18. Weiland O et al (2012) Therapeutic DNA vaccination using in vivo electroporation followed by standard of care therapy in patients with genotype 1 chronic hepatitis C. Mol Ther 21:1796–1805

    Article  Google Scholar 

  19. Keane-Myers AM et al (2014) DNA electroporation of multi-agent vaccines conferring protection against select agent challenge: TriGrid delivery system. Methods Mol Biol 1121:325–336

    Article  PubMed  Google Scholar 

  20. Dolter KE et al (2011) Immunogenicity, safety, biodistribution and persistence of ADVAX, a prophylactic DNA vaccine for HIV-1, delivered by in vivo electroporation. Vaccine 29:795–803

    Article  CAS  PubMed  Google Scholar 

  21. Kalams SA et al (2013) Safety and comparative immunogenicity of an HIV-1 DNA vaccine in combination with plasmid interleukin 12 and impact of intramuscular electroporation for delivery. J Infect Dis 208:818–829

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Vasan S et al (2011) In vivo electroporation enhances the immunogenicity of an HIV-1 DNA vaccine candidate in healthy volunteers. PLoS ONE 6:e19252

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Klein TM et al (1987) High-velocity microprojectiles for delivering nucleic acids into living cells. Nature 327:70–73

    Article  CAS  Google Scholar 

  24. Gill HS et al (2010) Cutaneous vaccination using microneedles coated with hepatitis C DNA vaccine. Gene Ther 17:811–814

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

Much of the work described herein has been funded by Swedish Science Council, the Swedish Cancer Foundation, the Stockholm County Council, Karolinska Institutet, and Chrontech Pharma.

Conflict of interest

MS is a board member of Chrontech which holds the commercial rights to the NS3/4A-based DNA vaccine.

Ethical standard

All studies discussed herein reported on clinical trials that had been approved by the appropriate ethical committees and government agencies.

Author information

Authors and Affiliations

  1. Division of Clinical Microbiology, F68, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86, Stockholm, Sweden

    Matti Sällberg, Lars Frelin, Gustaf Ahlén & Margaret Sällberg-Chen

  2. Department of Dental Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86, Stockholm, Sweden

    Margaret Sällberg-Chen

Authors
  1. Matti Sällberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lars Frelin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gustaf Ahlén
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Margaret Sällberg-Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Matti Sällberg.

Additional information

This article is part of the special issue “Therapeutic vaccination in chronic hepatitis B—approaches, problems, and new perspectives.”

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sällberg, M., Frelin, L., Ahlén, G. et al. Electroporation for therapeutic DNA vaccination in patients. Med Microbiol Immunol 204, 131–135 (2015). https://doi.org/10.1007/s00430-014-0384-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00430-014-0384-8

Keywords

Search

Navigation