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

• Published in: Journal of allergy and clinical immunology 2013-01, Vol.131 (1), p.213-221.e5
• Main Authors: Liu, Yu, MD, PhD, Sun, Yongtao, MD, PhD, Chang, Lee-Jah, MD, Li, Newton, MD, Li, Huabin, MD, PhD, Yu, Yanni, BSc, Bryce, Paul J., PhD, Grammer, Leslie C., MD, Schleimer, Robert P., PhD, Zhu, Daocheng, MD, PhD
• Format: Article
• Language: English
• Subjects: 2S Albumins, Plant - chemistry; 2S Albumins, Plant - genetics; 2S Albumins, Plant - immunology; Allergens - immunology; Allergic diseases; Allergy and Immunology; anaphylaxis; Anaphylaxis - immunology; Anaphylaxis - prevention & control; Animals; Antigens, Plant - chemistry; Antigens, Plant - genetics; Antigens, Plant - immunology; Arachis - immunology; basophils; Basophils - immunology; Basophils - metabolism; Biological and medical sciences; Cell Degranulation - immunology; Desensitization, Immunologic; Digestive allergic diseases; Disease Models, Animal; Female; Food allergy; Fundamental and applied biological sciences. Psychology; Fundamental immunology; fusion protein; Glycoproteins - chemistry; Glycoproteins - genetics; Glycoproteins - immunology; Histamine Release - immunology; Humans; Immunoglobulin E - immunology; Immunopathology; immunotherapy; Inflammation - immunology; Inflammation - prevention & control; mast cells; Medical sciences; Mice; Mice, Transgenic; peanut; Peanut Hypersensitivity - genetics; Peanut Hypersensitivity - immunology; Peanut Hypersensitivity - prevention & control; Plant Extracts - immunology; Receptors, IgG - chemistry; Receptors, IgG - genetics; Receptors, IgG - immunology; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - immunology; Respiratory System - immunology; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2012.10.018

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 Fcγ1. We tested the Ara h 2–Fcγ fusion protein (AHG2)'s function in purified human basophils. Transgenic mice expressing human FcϵRIα 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 hFcϵRIα 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 FcγRII. Conclusion AHG2 inhibited peanut-specific IgE-mediated allergic reactions in vitro and in vivo . Linking specific peanut allergen to Fcγ can provide a new approach for the allergen immunotherapy of peanut allergy.