RESEARCH ARTICLE


Ear Pinna: A Privileged DNA Electroporation Site for Inducing Strong Th1 Immune Responses



Jing Ni1, Britta Nolte1, Gaëlle Vandermeulen2, Veronique Preat2, Daniel Scherman3, Volker Schirrmacher1, Philippe Fournier*, 1
1 Division of Cellular Immunology, German Cancer Research Center, Heidelberg, Germany
2 Université catholique de Louvain, Department of Pharmaceutics, UCL73.20, 1200 Brussels, Belgium
3 Inserm, U640, Paris, F-75006 France; CNRS, UMR8151, Paris, F-75006 France; Université Paris Descartes, Faculté de Pharmacie, Chemical and Genetic Pharmacology Laboratory, Paris, F-75270 France; Ecole Nationale Supérieure de Chimie de Paris, Paris, F-75005 France


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© 2009 Ni et al.;

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Fax: +49 6221 424962; E-mail: p.fournier@dkfz.de


Abstract

DNA vaccination appears a very attractive approach for inducing immune responses towards the encoded antigen, but studies in large animals and in humans revealed weaknesses of such responses. In this study, we evaluated a new approach based on a new device combining DNA vaccination with electroporation (EP) at the ear pinna site. Under optimal EP conditions, the expression of the DNA encoded antigen and the induced immune responses were considerably increased. Very interestingly, DNA vaccination using EP at the ear pinna induced much stronger cellular immune responses than at the flank skin although antigen expression was similar at both sites. As compared to vaccination at the ear pinna without EP, IFN-􀀁 but not IL-4 production by splenocytes from immunized mice was significantly enhanced. In contrast, IL-4 but not IFN-􀀁 production was increased by EP at the flank skin. The vaccination site of the ear pinna combined with EP route even provided therapeutic effects in a mouse tumor model.

In conclusion, this study highlights the ear pinna as a privileged site for the induction of strong Th1 polarized cellular immunity against a defined antigen when combining DNA vaccination with EP.

Keywords: Antigen Expression, Immunization, Electroporation, vaccination, Tumor Therapy.