Development of asthma vaccines by manipulating enzyme activity of protease allergen 3590

Abstract Description Allergic asthma is a chronic inflammatory airway disease with recurrent airway obstruction and wheezing. Among various environmental allergens, the proteases derived from house dust mites, fungi, and pollens are well-characterized for their enzymatic activity triggering T helper type 2 (Th2) responses. In this study, by manipulating the protease activity of Aspergillus oryzae protease (AP) allergen, we secured fundamental know-how to develop a novel asthma vaccine called mutant AP (MutAP), which can control the differentiation of Th cells and induce immune tolerance. When pretreated intranasally, MutAP prevented the main asthma symptoms by inducing immune tolerance through regulatory T (Treg) cells. To confirm the mechanism of action, first, we depleted the alveolar macrophages (AMs) which are known to induce Treg cells in the airway and their dedication to immune tolerance. Secondly, inactive MutAP, deprived of its protease activity, lost the ability to damage epithelial cells and secrete alarmins. Among three alarmins, we identified IL-33 as the most critical, functioning as an inducer of allergic responses even with inactivated allergens. In conclusion, eliminating the protease activity from the original allergen led to the genus-specific vaccination effects against asthmatic allergen via Treg and AM in the absence of IL-33. Based on these results, we propose to develop a novel vaccine to prevent allergic asthma. Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)