title: Blockade of peanut allergy with a novel Ara h 2-Fcγ fusion protein in mice.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Yongtao
authors.initials: Y
authors.lastname: Sun
authors.forename: Lee-Jah
authors.initials: LJ
authors.lastname: Chang
authors.forename: Newton
authors.initials: N
authors.lastname: Li
authors.forename: Huabin
authors.initials: H
authors.lastname: Li
authors.forename: Yanni
authors.initials: Y
authors.lastname: Yu
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Bryce
authors.forename: Leslie C
authors.initials: LC
authors.lastname: Grammer
authors.forename: Robert P
authors.initials: RP
authors.lastname: Schleimer
authors.forename: Daocheng
authors.initials: D
authors.lastname: Zhu
mesh_terms: D055516:2S Albumins, Plant / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D000485:Allergens / Q000276:immunology; D000707:Anaphylaxis / Q000276:immunology / Q000517:prevention & control; D000818:Animals; D052179:Antigens, Plant / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D010367:Arachis / Q000276:immunology; D001491:Basophils / Q000276:immunology / Q000378:metabolism; D015550:Cell Degranulation / Q000276:immunology; D003888:Desensitization, Immunologic; D004195:Disease Models, Animal; D005260:Female; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006636:Histamine Release / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D008822:Mice, Transgenic; D021183:Peanut Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D010936:Plant Extracts / Q000276:immunology; D017452:Receptors, IgG / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000276:immunology*; D012137:Respiratory System / Q000276:immunology
chemical_list: D055516:2S Albumins, Plant; D000485:Allergens; D052179:Antigens, Plant; C500890:Ara h 2 allergen, Arachis hypogaea; D006023:Glycoproteins; D010936:Plant Extracts; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins; D007073:Immunoglobulin E