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Transcutaneous Anti-Influenza Vaccination Promotes Both CD4 and CD8 T Cell Immune Responses in Humans¹

Annika Vogt^2,3,*, Brice Mahé^2,, Dominique Costagliola, Olivia Bonduelle, Sabrina Hadam^*, Gregor Schaefer^*, Hans Schaefer^*, Christine Katlama, Wolfram Sterry^*, Brigitte Autran, Ulrike Blume-Peytavi^2,* and Béhazine Combadiere^2,3,

^* Clinical Research Center for Hair and Skin Physiology, Department of Dermatology and Allergy, Charité Universitätsmedizin Berlin, Berlin, Germany; and Institut National de Santé et de Recherche Médicale U543 and Université Pierre et Marie Curie, Laboratoire d’Immunologie Cellulaire, Institut National de Santé et de Recherche Médicale U720 and Université Pierre et Marie Curie, and Hôpital Pitié Salpêtrière, Service des Maladies Infectieuses, Paris, France

Induction of T cell responses has become one of the major goals in therapeutic vaccination against viral diseases and cancer. The use of the skin as target organ for vaccine has been spurred by recent implication of epithelial dendritic cells in CD8 cell cross-priming and suggests that vaccination via the transcutaneous (TC) route may be relevant in the induction of cellular immune responses. We have previously shown that TC application of nanoparticles, on human skin explants, allows targeting of epidermal dendritic cells, possibly via hair follicles. In this study, we have investigated cellular immune responses against an influenza protein-based vaccine by TC vaccination, compared with i.m. vaccination in humans. In this study on 11 healthy volunteers, we found that a newly developed protocol based on cyanocrylate skin surface stripping induced a significant increase in IFN-producing T cells specific for influenza vaccine by ELISPOT assays. Interestingly, TC vaccination induced both effector CD4 and CD8 T cell responses, whereas i.m. injection induced strong effector CD4 in the absence of CD8 T cells, as assessed by intracellular cytokine staining and tetramer analyses. This study proposes new perspectives for the development of vaccination strategies that trigger T cell immune responses in humans.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Objectifs Recherches Vaccins Syndrome d’Immuno-Deficience Acquis. B.M. was supported by a grant from the Ministère de la Recherche et des Technologies. B.C. is a recipient of Young Investigator Awards of the Agence Nationale de Recherche.

² A.V., B.M., U.B.-P., and B.C. participated equally in this work.

³ Address correspondence and reprint requests to Dr. Annika Vogt, Clinical Research Center for Hair and Skin Physiology, Department of Dermatology and Allergy, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. E-mail address: annika.vogt{at}charite.de or Dr. Béhazine Combadiere, and Institut National de la Santé et de la Recherche Médicale U543, Lab d’Immunologie Cellulaire, 91 Boulevard de l’Hopital, 75634 Paris Cedex 13, France. E-mail address: combadie{at}ccr.jussieu.fr

⁴ Abbreviations used in this paper: DC, dendritic cell; TC, transcutaneous; CSSS, cyanoacrylate skin surface stripping; SFU, spot-forming unit; RT, room temperature; LC, Langerhans cell.