Subcutaneous immunotherapy with purified Der p1 and 2 suppresses type-2 immunity in a murine asthma model

Abstract

Allergen-specific immunotherapy can induce long-term suppression of allergic symptoms, reduce medication use and prevent exacerbations of allergic rhinitis and asthma. Current treatment is based on crude allergen extracts, which contain immunostimulatory components such as β-glucans, chitins and endotoxin. Use of purified or recombinant allergens might therefore increase efficacy of treatment. Here, we test application of purified natural group 1 and 2 allergens from Dermatophagoides pteronyssinus (Der p) for subcutaneous immunotherapy (SCIT) treatment in a house dust mite (HDM) driven mouse model of allergic asthma.

HDM-sensitized mice received SCIT with crude HDM extract, a mixture of purified Der p1 and 2 (DerP1/2), or placebo. Upon challenges, we measured specific immunoglobulin responses, allergen-induced ear swelling (ESR), airway hyperresponsiveness (AHR) and inflammation in broncho-alveolar lavage fluid (BAL) and lung tissue.

ESR measurement shows suppression of early allergic response in HDM- and DerP1/2-SCIT treated mice. Both HDM-SCIT and DerP1/2-SCIT are able to suppress AHR and eosinophilic inflammation. In contrast, only DerP1/2-SCIT is able to significantly suppress type-2 cytokines in lung tissue and BAL fluid. Moreover, DerP1/2-SCIT treatment is uniquely able suppress CCL20 and showed a trend towards suppression of IL-33, CCL17 and eotaxin levels in lung tissue.

Taken together, these data show that purified DerP1/2-SCIT is able to not only suppress AHR and inflammation, but also has superior activity towards suppression of Th2 cells and HDM-induced activation of lung structural cells including airway epithelium. We postulate that treatment with purified natural major allergens derived from HDM will likely increase clinical efficacy of SCIT.

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