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  • Title: Improvement of sublingual immunotherapy efficacy with a mucoadhesive allergen formulation.
    Author: Razafindratsita A, Saint-Lu N, Mascarell L, Berjont N, Bardon T, Betbeder D, Van Overtvelt L, Moingeon P.
    Journal: J Allergy Clin Immunol; 2007 Aug; 120(2):278-85. PubMed ID: 17531296.
    Abstract:
    BACKGROUND: Sublingual immunotherapy is a noninvasive and efficacious treatment of type I respiratory allergies. A murine model of sublingual immunotherapy is needed to understand better the immune mechanisms involved in successful immunotherapy and to assess second-generation candidate vaccines. OBJECTIVE: Herein, we developed a therapeutic murine model of sublingual immunotherapy in which we document the value of mucoadhesive formulations to enhance treatment efficacy. METHODS: BALB/c mice were sublingually treated with soluble or formulated ovalbumin before or after sensitization with ovalbumin. Airways hyperresponsiveness and lung inflammation were assessed by whole-body plethysmography and lung histology, respectively. Humoral and cellular immune responses were monitored by ELISA and ELISPOT techniques. RESULTS: Prophylactic sublingual administration of ovalbumin completely prevents airways hyperresponsiveness as well as IL-5 secretion and IgE induction. Therapeutic administration of ovalbumin as a solution via either the sublingual or oral route has a limited efficacy. In contrast, sublingual application of ovalbumin formulated with maltodextrin to enhance mucosal adhesion results in a major reduction of established airways hyperresponsiveness, lung inflammation, and IL-5 production in splenocytes. This mucoadhesive formulation significantly enhances ovalbumin-specific T-cell proliferation in cervical but not mesenteric lymph nodes, and IgA production in the lungs. CONCLUSION: A mucoadhesive maltodextrin formulation of ovalbumin enhances priming of the local mucosal immune system and tolerance induction via the sublingual route. CLINICAL IMPLICATIONS: Mucoadhesive formulations offer the opportunity to improve dramatically sublingual immunotherapy in human beings, most particularly by simplifying immunization schemes.
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