Therapeutic intranasal instillation of allergen-loaded microbubbles suppresses experimental allergic asthma in mice

Despite proven efficiency, subcutaneous immunotherapy for aeroallergens is impaired by the duration of the protocol, the repeated injections and potential side-effects associated with the doses of allergen administered. Intranasal delivery of immunotherapeutic agents may overcome several of these drawbacks, provided that an efficient allergen delivery vehicle can be identified. This study evaluates whether intranasally delivered gas-filled microbubble (MB)-associated ovalbumin (OVA), used as a model allergen, can serve as a therapeutic treatment in a mouse model of established allergic asthma. Lung and systemic production of pro-tolerogenic markers, including Foxp3+ CD4 T cells, IL-10, and TGF-β, as well as the Th1-type cytokine IFN-γ, was observed after intranasal immunization with OVA-MB. Post-treatment, aerosol-sensitized mice exhibited the same pattern of markers. Moreover, decrease of eosinophils and neutrophils in BALs, lower frequencies of Th2 cytokine- and IL-17-producing CD4 T cells in lungs and reduced specific IgE in BALs and sera after allergen challenge were observed. Concomitantly, lung resistance and mucus production diminished in OVA-MB-treated animals. Thus, therapeutic intranasal administration of OVA-MBs in established experimental allergic asthma allows modulating pathology-associated immune and physiological parameters usually triggered after exposure to the allergen.