Pharmaceutical Research

, Volume 26, Issue 7, pp 1745–1751 | Cite as

Effect of Tape Stripping and Adjuvants on Immune Response After Intradermal DNA Electroporation

  • Gaëlle Vandermeulen
  • Liévin Daugimont
  • Hervé Richiardi
  • Marie-Lise Vanderhaeghen
  • Nathalie Lecouturier
  • Bernard Ucakar
  • Véronique Préat
Research Paper
First Online:
Received:
Accepted:

Abstract

Purpose

DNA vaccines require both efficient delivery methods and appropriate adjuvants. Based on their mechanisms of action, we hypothesised that some adjuvants could enhance vaccine immunogenicity or direct the response towards Th1 profile after intradermal DNA electroporation.

Methods

After intradermal electroporation of plasmid DNA encoding luciferase, mice received hyaluronidase, imiquimod, monophosphoryl lipid A or were tape stripped in order to modulate the immune response against the encoded protein. We measured total immunoglobulin G, IgG1, IgG2a titres and the cytokines produced by splenocyte cultures to assess both humoral and cellular response. The effect of tape stripping on the response against intradermally delivered ovalbumin protein was also assessed.

Results

Neither hyaluronidase nor imiquimod improved the immune response against the encoded luciferase. Monophosphoryl lipid A did not modify the cytokines production but increased the anti-luciferase IgG2a titres. Tape stripping significantly increased anti-luciferase IgG2a and IFN-γ responses. It also enhanced the humoral response after intradermal injection of the ovalbumin protein.

Conclusions

Tape stripping is able to increase the Th1 immune response against both DNA and protein vaccines. Therefore, tape stripping appears to have interesting adjuvant effect on intradermal vaccination.

KEY WORDS

adjuvant DNA vaccine electroporation skin 
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Notes

Acknowledgements

This research was supported by the European Commission under the 6th framework under the grant MOLEDA and by the FRSM (Fonds de la Recherche Scientifique Médicale, Belgium). Gaëlle Vandermeulen is FNRS Research Fellow (Fonds National de la Recherche Scientifique, Belgium).

References

  1. 1.
    Debenedictis C, Joubeh S, Zhang G, Barria M, Ghohestani RF. Immune functions of the skin. Clin Dermatol. 2001;19:573–85. doi: 10.1016/S0738-081X(00)00173-5.PubMedCrossRefGoogle Scholar
  2. 2.
    Cemazar M, Sersa G. Electrotransfer of therapeutic molecules into tissues. Curr Opin Mol Ther. 2007;9:554–62.PubMedGoogle Scholar
  3. 3.
    Pavselj N, Préat V. DNA electrotransfer into the skin using a combination of one high- and one low-voltage pulse. J Control Release. 2005;106:407–15. doi: 10.1016/j.jconrel.2005.05.003.PubMedCrossRefGoogle Scholar
  4. 4.
    Drabick JJ, Glasspool-Malone J, King A, Malone RW. Cutaneous transfection and immune responses to intradermal nucleic acid vaccination are significantly enhanced by in vivo electropermeabilization. Mol Ther. 2001;3:249–55. doi: 10.1006/mthe.2000.0257.PubMedCrossRefGoogle Scholar
  5. 5.
    Glasspool-Malone J, Somiari S, Drabick JJ, Malone RW. Efficient nonviral cutaneous transfection. Mol Ther. 2000;2:140–6. doi: 10.1006/mthe.2000.0107.PubMedCrossRefGoogle Scholar
  6. 6.
    Vandermeulen G, Staes E, Vanderhaeghen ML, Bureau MF, Scherman D, Préat V. Optimisation of intradermal DNA electrotransfer for immunisation. J Control Release. 2007;124:81–7. doi: 10.1016/j.jconrel.2007.08.010.PubMedCrossRefGoogle Scholar
  7. 7.
    Pedron-Mazoyer S, Plouet J, Hellaudais L, Teissie J, Golzio M. New anti angiogenesis developments through electro-immunization: optimization by in vivo optical imaging of intradermal electro gene transfer. Biochim Biophys Acta. 2007;1770:137–42.PubMedGoogle Scholar
  8. 8.
    Guy B. The perfect mix: recent progress in adjuvant research. Nat Rev Microbiol. 2007;5:505–17. doi: 10.1038/nrmicro1681.PubMedCrossRefGoogle Scholar
  9. 9.
    Lodmell DL, Ray NB, Ulrich JT, Ewalt LC. DNA vaccination of mice against rabies virus: effects of the route of vaccination and the adjuvant monophosphoryl lipid A (MPL). Vaccine 2000;18:1059–66. doi: 10.1016/S0264-410X(99)00352-7.PubMedCrossRefGoogle Scholar
  10. 10.
    Zhang WW, Matlashewski G. Immunization with a Toll-like receptor 7 and/or 8 agonist vaccine adjuvant increases protective immunity against Leishmania major in BALB/c mice. Infect Immun. 2008;76:3777–83. doi: 10.1128/IAI.01527-07.PubMedCrossRefGoogle Scholar
  11. 11.
    McMahon JM, Signori E, Wells KE, Fazio VM, Wells DJ. Optimisation of electrotransfer of plasmid into skeletal muscle by pretreatment with hyaluronidase—increased expression with reduced muscle damage. Gene Ther. 2001;8:1264–70. doi: 10.1038/sj.gt.3301522.PubMedCrossRefGoogle Scholar
  12. 12.
    Mummert DI, Takashima A, Ellinger L, Mummert ME. Involvement of hyaluronan in epidermal Langerhans cell maturation and migration in vivo. J Dermatol Sci. 2003;33:91–7. doi: 10.1016/S0923-1811(03)00160-9.PubMedCrossRefGoogle Scholar
  13. 13.
    Mummert ME. Immunologic roles of hyaluronan. Immunol Res. 2005;31:189–206. doi: 10.1385/IR:31:3:189.PubMedCrossRefGoogle Scholar
  14. 14.
    Termeer CC, Hennies J, Voith U, Ahrens T, Weiss JM, Prehm P, Simon JC. Oligosaccharides of hyaluronan are potent activators of dendritic cells. J Immunol. 2000;165:1863–70.PubMedGoogle Scholar
  15. 15.
    Voelcker V, Gebhardt C, Averbeck M, Saalbach A, Wolf V, Weih F, et al. Hyaluronan fragments induce cytokine and metalloprotease upregulation in human melanoma cells in part by signalling via TLR4. Exp Dermatol. 2008;17:100–7. doi: 10.1111/j.1600-0625.2007.00638.x.PubMedCrossRefGoogle Scholar
  16. 16.
    Novak N, Yu CF, Bieber T, Allam JP. Toll-like receptor 7 agonists and skin. Drug News Perspect. 2008;21:158–65.PubMedGoogle Scholar
  17. 17.
    Gaspari AA. Mechanism of action and other potential roles of an immune response modifier. Cutis 2007;79:36–45.PubMedGoogle Scholar
  18. 18.
    Johnston D, Bystryn JC. Topical imiquimod is a potent adjuvant to a weakly-immunogenic protein prototype vaccine. Vaccine 2006;24:1958–65. doi: 10.1016/j.vaccine.2005.10.045.PubMedCrossRefGoogle Scholar
  19. 19.
    Dockrell DH, Kinghorn GR. Imiquimod and resiquimod as novel immunomodulators. J Antimicrob Chemother. 2001;48:751–5. doi: 10.1093/jac/48.6.751.PubMedCrossRefGoogle Scholar
  20. 20.
    Caglar K, Aybay C, Ataoglu H. Effect of monophosphoryl lipid A on antibody response to diphtheria toxin and its subunits. APMIS 2005;113:256–63. doi: 10.1111/j.1600-0463.2005.apm_03.x.PubMedCrossRefGoogle Scholar
  21. 21.
    Freytag LC, Clements JD. Mucosal adjuvants. Vaccine 2005;23:1804–13. doi: 10.1016/j.vaccine.2004.11.010.PubMedCrossRefGoogle Scholar
  22. 22.
    Martin M, Michalek SM, Katz J. Role of innate immune factors in the adjuvant activity of monophosphoryl lipid A. Infect Immun. 2003;71:2498–507. doi: 10.1128/IAI.71.5.2498-2507.2003.PubMedCrossRefGoogle Scholar
  23. 23.
    McAleer JP, Vella AT. Understanding how lipopolysaccharide impacts CD4 T-cell immunity. Crit Rev Immunol. 2008;28:281–99.PubMedGoogle Scholar
  24. 24.
    Kahlon R, Hu Y, Orteu CH, Kifayet A, Trudeau JD, Tan R, Dutz JP. Optimization of epicutaneous immunization for the induction of CTL. Vaccine 2003;21:2890–9. doi: 10.1016/S0264-410X(03)00141-5.PubMedCrossRefGoogle Scholar
  25. 25.
    Strid J, Callard R, Strobel S. Epicutaneous immunization converts subsequent and established antigen-specific T helper type 1 (Th1) to Th2-type responses. Immunology 2006;119:27–35. doi: 10.1111/j.1365-2567.2006.02401.x.PubMedCrossRefGoogle Scholar
  26. 26.
    Inoue J, Aramaki Y. Toll-like receptor-9 expression induced by tape-stripping triggers on effective immune response with CpG-oligodeoxynucleotides. Vaccine 2007;25:1007–13. doi: 10.1016/j.vaccine.2006.09.075.PubMedCrossRefGoogle Scholar
  27. 27.
    Liu L, Zhou X, Shi J, Xie X, Yuan Z. Toll-like receptor-9 induced by physical trauma mediates release of cytokines following exposure to CpG motif in mouse skin. Immunology 2003;110:341–7. doi: 10.1046/j.1365-2567.2003.01739.x.PubMedCrossRefGoogle Scholar
  28. 28.
    Termeer C, Benedix F, Sleeman J, Fieber C, Voith U, Ahrens T, et al. Oligosaccharides of Hyaluronan activate dendritic cells via toll-like receptor 4. J Exp Med. 2002;195:99–111. doi: 10.1084/jem.20001858.PubMedCrossRefGoogle Scholar
  29. 29.
    Bloquel C, Trollet C, Pradines E, Seguin J, Scherman D, Bureau MF. Optical imaging of luminescence for in vivo quantification of gene electrotransfer in mouse muscle and knee. BMC Biotechnol. 2006;6:16. doi: 10.1186/1472-6750-6-16.PubMedCrossRefGoogle Scholar
  30. 30.
    Forg P, von HP, Dalemans W, Schirrmacher V. Superiority of the ear pinna over muscle tissue as site for DNA vaccination. Gene Ther. 1998;5:789–97. doi: 10.1038/sj.gt.3300628.PubMedCrossRefGoogle Scholar
  31. 31.
    McCluskie MJ, Brazolot Millan CL, Gramzinski RA, Robinson HL, Santoro JC, Fuller JT, et al. Route and method of delivery of DNA vaccine influence immune responses in mice and non-human primates. Mol Med. 1999;5:287–300. doi: 10.1007/s0089490050287.PubMedCrossRefGoogle Scholar
  32. 32.
    Vandermeulen G, Daugimont L, Préat V. DNA transfer in the skin. In Walters KA, Roberts MS, editors. Dermatologic, cosmeceutic, and cosmetic development: therapeutic and novel approaches. New York, London: Informa; 2008, p. 537–55.Google Scholar
  33. 33.
    Weiss R, Scheiblhofer S, Freund J, Ferreira F, Livey I, Thalhamer J. Gene gun bombardment with gold particles displays a particular Th2-promoting signal that over-rules the Th1-inducing effect of immunostimulatory CpG motifs in DNA vaccines. Vaccine 2002;20:3148–54. doi: 10.1016/S0264-410X(02)00250-5.PubMedCrossRefGoogle Scholar
  34. 34.
    Zhou X, Zheng L, Liu L, Xiang L, Yuan Z. T helper 2 immunity to hepatitis B surface antigen primed by gene-gun-mediated DNA vaccination can be shifted towards T helper 1 immunity by codelivery of CpG motif-containing oligodeoxynucleotides. Scand J Immunol. 2003;58:350–7. doi: 10.1046/j.1365-3083.2003.01310.x.PubMedCrossRefGoogle Scholar
  35. 35.
    Hirao LA, Wu L, Khan AS, Satishchandran A, Draghia-Akli R, Weiner DB. Intradermal/subcutaneous immunization by electroporation improves plasmid vaccine delivery and potency in pigs and rhesus macaques. Vaccine 2008;26:440–8. doi: 10.1016/j.vaccine.2007.10.041.PubMedCrossRefGoogle Scholar
  36. 36.
    Jiang W, Reich CF, Pisetsky DS. In vitro assay of immunostimulatory activities of plasmid vectors. Methods Mol Med. 2006;127:55–70.PubMedGoogle Scholar
  37. 37.
    Coban C, Koyama S, Takeshita F, Akira S, Ishii KJ. Molecular and cellular mechanisms of DNA vaccines. Hum Vaccin. 2008;4:453–6.PubMedGoogle Scholar
  38. 38.
    Sawamura D, Abe R, Goto M, Akiyama M, Hemmi H, Akira S, Shimizu H. Direct injection of plasmid DNA into the skin induces dermatitis by activation of monocytes through toll-like receptor 9. J Gene Med. 2005;7:664–71. doi: 10.1002/jgm.709.PubMedCrossRefGoogle Scholar
  39. 39.
    Gronevik E, Mathiesen I, Lomo T. Early events of electroporation-mediated intramuscular DNA vaccination potentiate Th1-directed immune responses. J Gene Med. 2005;7:1246–54. doi: 10.1002/jgm.760.PubMedCrossRefGoogle Scholar
  40. 40.
    Zuber AK, Brave A, Engstrom G, Zuber B, Ljungberg K, Fredriksson M, et al. Topical delivery of imiquimod to a mouse model as a novel adjuvant for human immunodeficiency virus (HIV) DNA. Vaccine 2004;22:1791–8. doi: 10.1016/j.vaccine.2003.10.051.PubMedCrossRefGoogle Scholar
  41. 41.
    Partidos CD, Muller S. Decision-making at the surface of the intact or barrier disrupted skin: potential applications for vaccination or therapy. Cell Mol Life Sci. 2005;62:1418–24. doi: 10.1007/s00018-005-4529-1.PubMedCrossRefGoogle Scholar
  42. 42.
    Frerichs DM, Ellingsworth LR, Frech SA, Flyer DC, Villar CP, Yu J, et al. Controlled, single-step, stratum corneum disruption as a pretreatment for immunization via a patch. Vaccine 2008;26:2782–7. doi: 10.1016/j.vaccine.2008.02.070.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Gaëlle Vandermeulen
    • 1
  • Liévin Daugimont
    • 1
  • Hervé Richiardi
    • 1
  • Marie-Lise Vanderhaeghen
    • 1
  • Nathalie Lecouturier
    • 1
  • Bernard Ucakar
    • 1
  • Véronique Préat
    • 1
  1. 1.Université catholique de LouvainUnité de Pharmacie GaléniqueBrusselsBelgium

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