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Murine intestinal M-cells express alpha-L-fucose residues. We constructed alpha-L-fucose-targeting particles for oral immunotherapy of IgE-mediated allergy. Poly(D,L-lactic-co-glycolic acid)-microspheres were loaded with birch pollen allergens, and functionalised with the alpha-L-fucose specific Aleuria aurantia lectin (AAL). The AAL-microspheres had a size of 1-3 microm, protected the entrapped allergens from gastric degradation and released 46.6+/-1.3% allergen over 21 days in vitro. Oral gavages of AAL-particles to naive BALB/c mice induced birch pollen-specific IgG2a, but not IgG1 antibodies. We conclude that targeting allergens to alpha-L-fucose-receptor bearing cells using AAL-microspheres induces specific Th1-antibody responses possibly counteracting Th2-dominated allergy, and therefore provides a potentially useful formulation for oral immunotherapy.