Intranasal delivery of allergen in a nanoemulsion adjuvant inhibits allergen- specific reactions in mouse models of allergic airway disease

Abstract

BackgroundAtopic diseases are an increasing problem that involve both immediate hypersensitivity reactions mediated by IgE and unique cellular inflammation. Many forms of specific immunotherapy involve the administration of allergen to suppress allergic immune responses but are focused on IgE- mediated reactions. In contrast, the effect of allergen- specific immunotherapy on allergic inflammation is complex, not entirely consistent and not well understood. We have previously demonstrated the ability of allergen administered in a nanoemulsion (NE) mucosal adjuvant to suppress IgE- mediated allergic responses and protect from allergen challenge in murine food allergy models. This activity was associated with decreases in allergen- specific IL- 10 and reductions in allergic cytokines and increases in regulatory T cells.ObjectiveHere, we extend these studies to using 2 distinct models, the ovalbumin (OVA) and cockroach (CRA) models of allergic airway disease, which are based predominantly on allergic inflammation.MethodsAcute or chronic allergic airway disease was induced in mice using ovalbumin and cockroach allergen models. Mice received three therapeutic immunizations with allergen in NE, and reactivity to airway challenge was determined.ResultsTherapeutic immunization with cockroach or OVA allergen in NE markedly reduced pathology after airway challenge. The 2 models demonstrated protection from allergen challenge- induced pathology that was associated with suppression of Th2- polarized immune responses in the lung. In addition, the reduction in ILC2 numbers in the lungs of allergic mice along with reduction in epithelial cell alarmins, IL- 25 and IL- 33, suggests an overall change in the lung immune environment induced by the NE immunization protocol.Conclusions and Clinical RelevanceThese results demonstrate that suppression of allergic airway inflammation and bronchial hyper- reactivity can be achieved using allergen- specific immunotherapy without significant reductions in allergen- specific IgE and suggest that ILC2 cells may be critical targets for this activity.The ability of intranasal vaccines to modulate allergic immune responses and inflammation in the lung was studied in two distinct models of allergic airway disease. Mice were sensitized to ovalbumin or cockroach allergen and subsequently received three immunizations with allergen in nanoemulsion adjuvant. Nanoemulsion vaccines modulated the allergen- specific cytokine milieu in the lungs to suppress Th2 cytokine production, alarmin expression and recruitment of ILC2s. The immune modulation in the lungs was associated with protection from allergen challenge- induced inflammation and reactivity.