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Mendoza JM, Amante DH, Kichaev G, et al. Elucidating the Kinetics of Expression and Immune Cell Infiltration Resulting from Plasmid Gene Delivery Enhanced by Surface Dermal Electroporation. Vaccines (Basel). 2013;1(3):384-97doi: 10.3390/vaccines1030384.
Mendoza, J. M., Amante, D. H., Kichaev, G., Knott, C. L., Kiosses, W. B., Smith, T. R., Sardesai, N. Y., & Broderick, K. E. (2013). Elucidating the Kinetics of Expression and Immune Cell Infiltration Resulting from Plasmid Gene Delivery Enhanced by Surface Dermal Electroporation. Vaccines, 1(3), 384-97. https://doi.org/10.3390/vaccines1030384
Mendoza, Janess M, et al. "Elucidating the Kinetics of Expression and Immune Cell Infiltration Resulting from Plasmid Gene Delivery Enhanced by Surface Dermal Electroporation." Vaccines vol. 1,3 (2013): 384-97. doi: https://doi.org/10.3390/vaccines1030384
Mendoza JM, Amante DH, Kichaev G, Knott CL, Kiosses WB, Smith TR, Sardesai NY, Broderick KE. Elucidating the Kinetics of Expression and Immune Cell Infiltration Resulting from Plasmid Gene Delivery Enhanced by Surface Dermal Electroporation. Vaccines (Basel). 2013 Aug 28;1(3):384-97. doi: 10.3390/vaccines1030384. PMID: 26344120; PMCID: PMC4494224.
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Vaccines (Basel). 2013 Aug 28;1(3):384-97. doi: 10.3390/vaccines1030384.

Elucidating the Kinetics of Expression and Immune Cell Infiltration Resulting from Plasmid Gene Delivery Enhanced by Surface Dermal Electroporation.

Vaccines

Janess M Mendoza, Dinah H Amante, Gleb Kichaev, Christine L Knott, William B Kiosses, Trevor R F Smith, Niranjan Y Sardesai, Kate E Broderick

Affiliations

  1. Inovio Pharmaceuticals Inc., 1787 Sentry Parkway West, Building 18, Suite 400, Blue Bell, PA 19422, USA.
  2. The Scripps Research Institute, Core Microscopy Facility, 10550 North Torrey Pines Rd, La Jolla, CA 92037, USA.
  3. Inovio Pharmaceuticals Inc., 1787 Sentry Parkway West, Building 18, Suite 400, Blue Bell, PA 19422, USA. [email protected].

PMID: 26344120 PMCID: PMC4494224 DOI: 10.3390/vaccines1030384

Abstract

The skin is an attractive tissue for vaccination in a clinical setting due to the accessibility of the target, the ease of monitoring and most importantly the immune competent nature of the dermal tissue. While skin electroporation offers an exciting and novel future methodology for the delivery of DNA vaccines in the clinic, little is known about the actual mechanism of the approach and the elucidation of the resulting immune responses. To further understand the mechanism of this platform, the expression kinetics and localization of a reporter plasmid delivered via a surface dermal electroporation (SEP) device as well as the effect that this treatment would have on the resident immune cells in that tissue was investigated. Initially a time course (day 0 to day 21) of enhanced gene delivery with electroporation (EP) was performed to observe the localization of green fluorescent protein (GFP) expression and the kinetics of its appearance as well as clearance. Using gross imaging, GFP expression was not detected on the surface of the skin until 8 h post treatment. However, histological analysis by fluorescent microscopy revealed GFP positive cells as early as 1 h after plasmid delivery and electroporation. Peak GFP expression was observed at 24 h and the expression was maintained in skin for up to seven days. Using an antibody specific for a keratinocyte cell surface marker, reporter gene positive keratinocytes in the epidermis were identified. H&E staining of treated skin sections demonstrated an influx of monocytes and granulocytes at the EP site starting at 4 h and persisting up to day 14 post treatment. Immunological staining revealed a significant migration of lymphocytic cells to the EP site, congregating around cells expressing the delivered antigen. In conclusion, this study provides insights into the expression kinetics following EP enhanced DNA delivery targeting the dermal space. These findings may have implications in the future to design efficient DNA vaccination strategies for the clinic.

Keywords: DNA vaccine; electroporation; infiltration; intradermal; kinetics

References

  1. Hum Gene Ther Methods. 2012 Jun;23(3):157-68 - PubMed
  2. Vaccine. 2011 Sep 9;29(39):6781-4 - PubMed
  3. Cancer Immunol Immunother. 2012 Nov;61(11):2161-70 - PubMed
  4. Gene Ther. 2007 Feb;14(3):275-80 - PubMed
  5. J Invest Dermatol. 1995 Jul;105(1 Suppl):25S-29S - PubMed
  6. Clin Vaccine Immunol. 2010 Sep;17(9):1381-9 - PubMed
  7. Biochem Biophys Res Commun. 1996 Mar 27;220(3):633-6 - PubMed
  8. J Virol. 2009 May;83(9):4624-30 - PubMed
  9. Contact Dermatitis. 2009 Jan;60(1):2-20 - PubMed
  10. Hum Vaccin Immunother. 2013 Oct;9(10):2246-52 - PubMed
  11. Curr Opin Immunol. 2011 Jun;23(3):421-9 - PubMed
  12. J Gene Med. 2005 Feb;7(2):218-27 - PubMed
  13. J Immunol. 2000 May 1;164(9):4635-40 - PubMed
  14. Hum Gene Ther. 2010 Mar;21(3):357-62 - PubMed
  15. Life Sci. 1997;60(3):163-72 - PubMed
  16. Gene Ther. 2007 Apr;14(7):553-64 - PubMed
  17. Gene Ther. 2011 Mar;18(3):258-65 - PubMed
  18. Clin Vaccine Immunol. 2012 Sep;19(9):1557-9 - PubMed
  19. Vaccine. 2008 Sep 19;26(40):5073-4 - PubMed
  20. PLoS One. 2009 Sep 30;4(9):e7226 - PubMed
  21. Vaccine. 2004 Jun 23;22(19):2489-93 - PubMed
  22. Hum Gene Ther. 2009 Nov;20(11):1291-307 - PubMed
  23. PLoS One. 2011;6(5):e19252 - PubMed
  24. J Infect Dis. 2011 Jan 1;203(1):95-102 - PubMed
  25. APMIS. 2003 Jul-Aug;111(7-8):725-40 - PubMed
  26. Hum Vaccin Immunother. 2012 Nov 1;8(11):1729-33 - PubMed
  27. Gene Ther. 1999 Apr;6(4):508-14 - PubMed
  28. Mol Ther. 2012 Jan;20(1):214-20 - PubMed
  29. Chem Soc Rev. 2006 Jan;35(1):52-67 - PubMed
  30. Biochim Biophys Acta. 2002 Aug 15;1572(1):1-9 - PubMed
  31. J Virol. 1998 Feb;72(2):1497-503 - PubMed
  32. PLoS One. 2011 Apr 29;6(4):e19181 - PubMed
  33. Mol Ther. 2006 Feb;13(2):320-7 - PubMed
  34. J Transl Med. 2013 Mar 08;11:62 - PubMed
  35. Vaccine. 2006 May 22;24(21):4503-9 - PubMed
  36. Vaccine. 2008 Jan 17;26(3):440-8 - PubMed
  37. Sci Transl Med. 2012 Oct 10;4(155):155ra138 - PubMed
  38. Hum Vaccin. 2011 Jan-Feb;7 Suppl:22-8 - PubMed

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