Background: Peanut allergy is a life-threatening condition for which new efficient and safe treatment is expected. We evaluated epicutaneous immunotherapy (EPIT) as a new alternative treatment for peanut allergy in sensitized mice. Methods: Sixty BALB/c mice were sensitized by gavages with peanut protein extract (PPE) mixed with cholera toxin. An epicutaneous delivery system, coated with 100 µg PPE (Viaskin®, DBV Technologies, Paris, France), was applied to intact skin every week during 48 h (EPIT; n = 20). This group was compared with sensitized mice treated with subcutaneous immunotherapy (SCIT; n = 20), untreated sensitized mice (sham, n = 20), and naive mice (naive; n = 20). After the 8-week treatment, a histamine release test, airway hyperreactivity measurement by plethysmography, and a resistance-compliance measurement after the challenge were performed. Blood and bronchoalveolar lavage were sampled for serology, cytokines, and cytology. Results: Specific IgE (sIgE) increased after sensitization in the EPIT (0.26 µg/ml) and SCIT (0.21 µg/ml) groups and decreased after treatment (0.09 µg/ml, p < 0.001 and 0.06 µg/ml, p < 0.001, respectively). The IgG1/IgG2a ratio decreased in the EPIT and SCIT groups versus the sham group (3.7; p < 0.001 and 2.7; p < 0.01 and 15.1, respectively). At the higher metacholine concentration, enhanced pause values were lower in the EPIT and SCIT groups than in the sham group (7.29, 6.74, and 10.99, p < 0.01, respectively), and did not differ from that of the naive group (5.06). Resistance-compliance was reversed in the treated groups versus the sham group (p < 0.001). IL-4, IL-5, IL-13, eotaxin, and eosinophils were reduced in the BAL of the EPIT and SCIT groups versus the sham group (p < 0.001). Conclusion: In peanut-sensitized mice, based on biological and physiological responses, EPIT is as efficient as subcutaneous treatment which is the reference method in immunotherapy.

Eigenmann PA: Future therapeutic options in food allergy. Allergy 2003;58:1217–1223.
Sicherer SH, Sampson HA: Peanut allergy: emerging concepts and approaches for an apparent epidemic. J Allergy Clin Immunol 2007;120:491–503.
Du Toit G, Katz Y, Sasieni P, Mesher D, Maleki SJ, Fisher HR, Fox AT, Turcanu V, Amir T, Zadik-Mnuhin G, Cohen A, Livne I, Lack G: Early consumption of peanuts in infancy is associated with a low prevalence of peanut allergy. J Allergy Clin Immunol 2008;122:984–991.
Greenberger PA, Ballow M, Casale TB, Platts-Mills TA, Sampson HA: Sublingual immunotherapy and subcutaneous immunotherapy: issues in the United States. J Allergy Clin Immunol 2007;120:1466–1468.
Bousquet J: Sublingual immunotherapy: validated. Allergy 2006;61:5–6.
Valenta R: The future of antigen-specific immunotherapy of allergy. Nat Rev Immunol 2002;2:446–453.
de Boissieu D, Dupont C: Sublingual immunotherapy for cow’s milk protein allergy: a preliminary report. Allergy 2006;61:1238–1239.
Longo G, Barbi B, Berti I, Meneghetti R, Pittalis A, Ronfani L, Ventura A: Specific oral tolerance induction in children with very severe cow’s milk-induced reactions. J Allergy Clin Immunol 2008;121:343–347.
Mondoulet L, Dioszeghy V, Ligouis M, Dhelft V, Dupont C, Benhamou PH: Epicutaneous immunotherapy on intact skin using a new delivery system in a murine model of allergy. Clin Exp Allergy 2010;40:659–667.
Sampson HA, Mendelson L, Rosen JP: Fatal and near-fatal anaphylactic reactions to food in children and adolescents. N Engl J Med 1992;327:380–384.
Bock SA, Munoz-Furlong A, Sampson HA: Fatalities due to anaphylactic reactions to foods. J Allergy Clin Immunol 2001;107:191–193.
Kalach N, Soulaines P, de Boissieu D, Dupont C: A pilot study of the usefulness and safety of a ready-to-use atopy patch test (Diallertest) versus a comparator (Finn Chamber) during cow’s milk allergy in children. J Allergy Clin Immunol 2005;116:1321–1326.
Lagranderie M, Abolhassani M, Vanoirbeek J, Lefort J, Nahori MA, Lapa E, Silva JR, Huerre M, Vargaftig B, Marchal G: Mycobacterium bovis BCG killed by extended freeze-drying reduces airway hyperresponsiveness in 2 animal models. J Allergy Clin Immunol 2008;121:471–478.
Li XM, Serebrisky D, Lee SY, Huang CK, Bardina L, Schofield BH, Stanley JS, Burks AW, Bannon GA, Sampson HA: A murine model of peanut anaphylaxis: T- and B-cell responses to a major peanut allergen mimic human responses. J Allergy Clin Immunol 2000;106:150–158.
Hamelmann E, Schwarze J, Takeda K, Oshiba A, Larsen GL, Irvin CG, Gelfand EW: Noninvasive measurement of airway responsiveness in allergic mice using barometric plethysmography. Am J Respir Crit Care Med 1997;156:766–775.
Vanoirbeek JA, Vanhooren HM, Nawrot TS, Nemery B, Hoet PH: How long do the systemic and ventilatory responses to toluene diisocyanate persist in dermally sensitized mice? J Allergy Clin Immunol 2008;121:456–463.
Vanoirbeek JA, Rinaldi M, De Vooght V, Haenen S, Bobic S, Gayan-Ramirez G, Hoet PH, Verbeken E, Decramer M, Nemery B, Janssens W: Noninvasive and invasive pulmonary function in mouse models of obstructive and restrictive respiratory diseases. Am J Respir Cell Mol Biol 2010;42:96–104.
Adel-Patient K, Bernard H, Ah-Leung S, Creminon C, Wal JM: Peanut- and cow’s milk-specific IgE, Th2 cells and local anaphylactic reaction are induced in Balb/c mice orally sensitized with cholera toxin. Allergy 2005;60:658–664.
von der Weid T, Bulliard C, Fritsche R: Suppression of specific and bystander IgE responses in a mouse model of oral sensitization to beta-lactoglobulin. Int Arch Allergy Immunol 2001;125:307–315.
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.
Strid J, Hourihane J, Kimber I, Callard R, Strobel S: Epicutaneous exposure to peanut protein prevents oral tolerance and enhances allergic sensitization. Clin Exp Allergy 2005;35:757–766.
Strid J, Thomson M, Hourihane J, Kimber I, Strobel S: A novel model of sensitization and oral tolerance to peanut protein. Immunology 2004;113:293–303.
Van Oosterhout AJ, Van Esch B, Hofman G, Hofstra CL, Van Ark I, Nijkamp FP, Kapsenberg ML, Savelkoul HF, Weller FR: Allergen immunotherapy inhibits airway eosinophilia and hyperresponsiveness associated with decreased IL-4 production by lymphocytes in a murine model of allergic asthma. Am J Respir Cell Mol Biol 1998;19:622–628.
Poulsen OM, Nielsen BR, Basse A, Hau J: Comparison of intestinal anaphylactic reactions in sensitized mice challenged with untreated bovine milk and homogenized bovine milk. Allergy 1990;45:321–326.
Li XM, Serebrisky D, Lee SY, Huang CK, Bardina L, Schofield BH, Stanley JS, Burks AW, Bannon GA, Sampson HA: A murine model of peanut anaphylaxis: T- and B-cell responses to a major peanut allergen mimic human responses. J Allergy Clin Immunol 2000;106:150–158.
Li XM, Kleiner G, Huang CK, Lee SY, Schofield B, Soter NA, Sampson HA: Murine model of atopic dermatitis associated with food hypersensitivity. J Allergy Clin Immunol 2001;107:693–702.
Li XM, Schofield BH, Huang CK, Kleiner GI, Sampson HA: A murine model of IgE-mediated cow’s milk hypersensitivity. J Allergy Clin Immunol 1999;103:206–214.
Spergel J, Mizoguchi E, Brewer JP, Martin TR, Bahn AK, Geha RS: Epicutaneous sensitization with protein antigen induces localized allergic dermatitis and hyperresponsiveness to methacholine after single exposure to aerosolized antigen in mice. J Clin Invest 1998;101:1614–1622.
Lundblad LK, Irvin CG, Adler A, Bates JH: A reevaluation of the validity of unrestrained plethysmography in mice. J Appl Physiol 2002;93:1198–1207.
Hoymann HG: New developments in lung function measurements in rodents. Exp Toxicol Pathol 2006;57(suppl 2):5–11.
Glaab T, Mitzner W, Braun A, Ernst H, Korolewitz R, Hohlfeld JM, Krug N, Hoymann HG: Repetitive measurements of pulmonary mechanics to inhaled cholinergic challenge in spontaneously breathing mice. J Appl Physiol 2004;97:1104–1111.
Turcanu V, Maleki SJ, Lack G: Characterization of lymphocyte responses to peanuts in normal children, peanut-allergic children, and allergic children who acquired tolerance to peanuts. J Clin Invest 2003;111:1065–1072.
Fulkerson PC, Rothenberg ME: Origin, regulation and physiological function of intestinal oeosinophils. Best Pract Res Clin Gastroenterol 2008;22:411–423.
Collins PD, Marleau S, Griffiths-Johnson DA, Jose PJ, Williams TJ: Cooperation between interleukin-5 and the chemokine eotaxin to induce eosinophil accumulation in vivo. J Exp Med 1995;82:1169–1174.
Wang Y, McCusker CT: Interleukin-13-dependent bronchial hyper-responsiveness following isolated upper-airway allergen challenge in a murine model of allergic rhinitis and asthma. Clin Exp Allergy 2005;35:1104–1111.
Senti G, Graf N, Haug S, Ruedi N, von Moos S, Sonderegger T, Johansen P, Kundig TM: Epicutaneous allergen administration as a novel method of allergen-specific immunotherapy. J Allergy Clin Immunol 2009;124:997–1002.
Dupont C, Kalach N, Soulaines P, Legoué-Morillon S, Benhamou PH: Cow’s milk epicutaneous immunotherapy in children: a pilot trial of safety, acceptability and impact on allergic reactivity. J Allergy Clin Immunol 2010;125:1165–1167.
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