title: Persistent protective effect of heat-killed Escherichia coli producing "engineered," recombinant peanut proteins in a murine model of peanut allergy.
abstract: BACKGROUND
  Peanut allergy (PNA) is a life-threatening food allergy for which there is no definitive treatment.
  
  
  OBJECTIVE
  We investigated the long-term immunomodulatory effect of heat-killed Escherichia coli producing engineered (mutated) Ara h1, 2, and 3 (HKE-MP123) administered rectally (pr) in a murine model of PNA.
  
  
  METHODS
  Peanut-allergic C3H/HeJ mice received 0.9 (low dose), 9 (medium dose), or 90 (high dose) microg HKE-MP123 pr, HKE-containing vector (HKE-V) alone, or vehicle alone (sham) weekly for 3 weeks. Mice were challenged 2 weeks later. A second and third challenge were performed at 4-week intervals.
  
  
  RESULTS
  After the first challenge, all 3 HKE-MP123 and HKE-V-treated groups exhibited reduced symptom scores (P <.01,.01,.05,.05, respectively) compared with the sham-treated group. Interestingly, only the medium- and high-dose HKE-MP123-treated mice remained protected for up to 10 weeks after treatment accompanied by a significant reduction of plasma histamine levels compared with sham-treated mice (P <.05 and.01, respectively). IgE levels were significantly lower in all HKE-MP123-treated groups (P <.001), being most reduced in the high-dose HKE-MP123-treated group at the time of each challenge. IL-4, IL-13, IL-5, and IL-10 production by splenocytes of high-dose HKE-MP123-treated mice were significantly decreased (P <.01;.001,.001, and.001, respectively), and IFN-gamma and TGF-beta production were significantly increased (P <.001 and.01, respectively) compared with sham-treated mice at the time of the last challenge.
  
  
  CONCLUSIONS
  Treatment with pr HKE-MP123 can induce long-term "downregulation" of peanut hypersensitivity, which might be secondary to decreased antigen-specific T(H)2 and increased T(H)1 and T regulatory cytokine production.
authors.affiliation: Department of Pediatrics, Mount Sinai School of Medicine, New York, NY 10029-6574, USA.
authors.forename: Xiu-Min
authors.initials: XM
authors.lastname: Li
authors.forename: Kamal
authors.initials: K
authors.lastname: Srivastava
authors.forename: Alexander
authors.initials: A
authors.lastname: Grishin
authors.forename: Chih-Kang
authors.initials: CK
authors.lastname: Huang
authors.forename: Brian
authors.initials: B
authors.lastname: Schofield
authors.forename: Wesley
authors.initials: W
authors.lastname: Burks
authors.forename: Hugh A
authors.initials: HA
authors.lastname: Sampson
mesh_terms: D055516:2S Albumins, Plant; D000485:Allergens / Q000008:administration & dosage*; D000818:Animals; D052179:Antigens, Plant; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D006023:Glycoproteins / Q000008:administration & dosage*; D006636:Histamine Release / Q000187:drug effects; D006358:Hot Temperature; D007073:Immunoglobulin E; D008565:Membrane Proteins; D051379:Mice; D008809:Mice, Inbred C3H; D021183:Peanut Hypersensitivity / Q000517:prevention & control*; D010940:Plant Proteins / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage; D055314:Seed Storage Proteins; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D055516:2S Albumins, Plant; D000485:Allergens; D052179:Antigens, Plant; C500889:Ara h 1 protein, Arachis hypogaea; C078642:Ara h II protein, Arachis hypogaea; D016207:Cytokines; D006023:Glycoproteins; D008565:Membrane Proteins; D010940:Plant Proteins; D011994:Recombinant Proteins; D055314:Seed Storage Proteins; C118207:allergen Ara h3; D007073:Immunoglobulin E