title: Anti-hIgE gene therapy of peanut-induced anaphylaxis in a humanized murine model of peanut allergy.
abstract: Peanuts are the most common food to provoke fatal or near-fatal anaphylactic reactions. Treatment with an anti-hIgE mAb is efficacious but requires frequent parenteral administration.
  
  
  
  Based on the knowledge that peanut allergy is mediated by peanut-specific IgE, we hypothesized that a single administration of an adeno-associated virus (AAV) gene transfer vector encoding for anti-hIgE would protect against repeated peanut exposure in the host with peanut allergy.
  
  
  
  We developed a novel humanized murine model of peanut allergy that recapitulates the human anaphylactic response to peanuts in NOD-scid IL2Rgammanullmice transferred with blood mononuclear cells from donors with peanut allergy and then sensitized with peanut extract. As therapy, we constructed an adeno-associated rh.10 serotype vector coding for a full-length, high-affinity, anti-hIgE antibody derived from the Fab fragment of the anti-hIgE mAb omalizumab (AAVrh.10anti-hIgE). In the reconstituted mice peanut-specific IgE was induced by peanut sensitization and hypersensitivity, and reactions were provoked by feeding peanuts to mice with symptoms similar to those of human subjects with peanut allergy.
  
  
  
  A single administration of AAVrh.10anti-hIgE vector expressed persistent levels of anti-hIgE. The anti-hIgE vector, administered either before sensitization or after peanut sensitization and manifestation of the peanut-induced phenotype, blocked IgE-mediated alterations in peanut-induced histamine release, anaphylaxis scores, locomotor activity, and free IgE levels and protected animals from death caused by anaphylaxis.
  
  
  
  If this degree of persistent efficacy translates to human subjects, AAVrh.10anti-hIgE could be an effective 1-time preventative therapy for peanut allergy and possibly other severe, IgE-mediated allergies.
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY.
authors.forename: Odelya E
authors.initials: OE
authors.lastname: Pagovich
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY; Department of Respiratory Medicine, West China Hospital, Sichuan University, Sichuan, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Chiuchiolo
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Kaminsky
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY.
authors.forename: Dolan
authors.initials: D
authors.lastname: Sondhi
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY.
authors.forename: Clarisse L
authors.initials: CL
authors.lastname: Jose
authors.affiliation: Departments of Internal Medicine and Pediatrics, Yale University School of Medicine, New Haven, Conn.
authors.forename: Christina C
authors.initials: CC
authors.lastname: Price
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY.
authors.forename: Sarah F
authors.initials: SF
authors.lastname: Brooks
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY; Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY.
authors.forename: Jason G
authors.initials: JG
authors.lastname: Mezey
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY. Electronic address: geneticmedicine@med.cornell.edu.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Crystal
mesh_terms: D000485:Allergens / Q000276:immunology*; D000707:Anaphylaxis / Q000276:immunology*; D000818:Animals; D010367:Arachis / Q000276:immunology*; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D021183:Peanut Hypersensitivity / Q000276:immunology*; D010936:Plant Extracts / Q000276:immunology* / Q000627:therapeutic use; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000485:Allergens; D016207:Cytokines; D010936:Plant Extracts; D007073:Immunoglobulin E
keywords: IgE; Peanut allergy; food allergy; gene therapy; mouse model; omalizumab