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Previously, we reported that TLR-2/MyD88-mediated airway tolerance could prevent Th2-type airway inflammation. Here, we investigated whether an airway-bound peptide vaccine can deliver the tolerogenic peptide to the airways and exert systemic immunomodulatory effects. In a mouse model of ovalbumin-induced airway allergic inflammation, we found that the tolerogenic peptide bound to an alum-based surface delivered airway tolerance by depleting lung dendritic cells (DCs) via TLR-2 and MyD88. Oral ingestion of the peptide also blocked eosinophilic airway inflammation in OVA-immunized mice. These results indicated that an airway-bound peptide vaccine co-delivered with IL-2 could induce airway tolerance and prevent eosinophilic airway inflammation. 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