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Intact skin and not stripped skin is crucial for the safety and efficacy of peanut epicutaneous immunotherapy (EPIT) in mice

Lucie Mondoulet1*, Vincent Dioszeghy1, Emilie Puteaux1, Mélanie Ligouis1, Véronique Dhelft1, Franck Letourneur2, Christophe Dupont3 and Pierre-Henri Benhamou1

Author Affiliations

1 DBV Technologies, Green Square, Bagneux, France

2 Institut Cochin, Université Paris Descartes, INSERM-U567, Paris, France

3 Hôpital Necker-Enfants Malades, Université Paris Descartes, Paris, France

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Clinical and Translational Allergy 2012, 2:22  doi:10.1186/2045-7022-2-22

Published: 12 November 2012

Abstract

Background

Epicutaneous immunotherapy (EPIT) on intact skin with an epicutaneous delivery system has already been used in preclinical and clinical studies. In epicutaneous vaccination and immunotherapy, the stripping of skin before application of the allergen is suggested to facilitate the passage of allergen through immune cells.

Objectives

The aim of this study was to compare the immunological response induced by EPIT performed on intact and stripped skin in a mouse model of peanut allergy.

Methods

After oral sensitization with peanut and cholera toxin, BALB/c mice were epicutaneously treated using an epicutaneous delivery system (Viaskin® (DBV Technologies, Paris) applied either on intact skin or on stripped skin. Following EPIT, mice received an exclusive oral peanut regimen, aimed at triggering esophageal and jejunal lesions. We assessed eosinophil infiltration by histology, mRNA expression in the esophagus, antibody levels and peripheral T-cell response.

Results

EPIT on intact skin significantly reduced Th2 immunological response (IgE response and splenocyte secretion of Th2 cytokines) as well as esophageal eosinophilia (2.7 ± 0.9, compared to Sham 19.9 ± 1.5, p < 0.01), mRNA expression of Th2 cytokines in tissue and intestinal villus sub-atrophia (2.9 ± 0.2 vs Sham, 2.1 ± 0.2, p < 0.05). By contrast, EPIT on stripped skin reinforced Th2 systemic immunological response as well as eosinophil infiltration (26.8 ± 15.1), mRNA expression of Th2 cytokines and duodenal villus/crypt-ratio (2.4 ± 0.3).

Conclusions

Epicutaneous allergen-specific immunotherapy needs the integrity of superficial layers of the stratum corneum to warranty safety of treatment and to induce a tolerogenic profile of the immune response.

Keywords:
Food allergy; Immunotherapy; Epicutaneous; Peanut