Blockade of peanut allergy with a novel Ara h 2-Fcγ fusion protein in mice

Background: Conventional immunotherapy for peanut allergy using crude peanut extracts is not recommended because of the unacceptably high risk of anaphylaxis. Allergen-specific immunotherapy is not currently undertaken for peanut allergy. Objectives: The objective of this study was to develop a novel peanut-human fusion protein to block peanut-induced anaphylaxis. Methods: We genetically designed and expressed a novel plant-human fusion protein composed of the major peanut allergen Ara h 2 and human IgG Fc gamma 1. We tested the Ara h 2-Fc gamma fusion protein (AHG2)'s function in purified human basophils. Transgenic mice expressing human Fc epsilon RI alpha and a murine peanut allergy model were used. Results: AHG2 inhibited histamine release induced by whole peanut extract (WPE) from basophils of patients with peanut allergy, whereas the fusion protein itself did not induce mediator release. AHG2 inhibited the WPE-induced, peanut-specific, IgE-mediated passive cutaneous anaphylaxis in hFc epsilon RI alpha transgenic mice. AHG2 also significantly inhibited acute anaphylactic reactivity, including the prototypical decrease in body temperature in WPE-sensitized mice challenged with crude peanut extract. Histologic evaluation of the airways showed that AHG2 decreased peanut-induced inflammation, whereas the fusion protein itself did not induce airway inflammation in peanut-sensitized mice. AHG2 did not exert an inhibitory effect in mice lacking Fc gamma RII. Conclusion: AHG2 inhibited peanut-specific IgE-mediated allergic reactions in vitro and in vivo. Linking specific peanut allergen to Fc gamma can provide a new approach for the allergen immunotherapy of peanut allergy. (J Allergy Clin Immunol 2013;131:213-21.)