Persistent protective effect of heat-killed Escherichia coli producing "engineered," recombinant peanut proteins in a murine model of peanut allergy.
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.
Li
Xiu-Min
XM
Department of Pediatrics, Mount Sinai School of Medicine, New York, NY 10029-6574, USA.
Srivastava
Kamal
K
Grishin
Alexander
A
Huang
Chih-Kang
CK
Schofield
Brian
B
Burks
Wesley
W
Sampson
Hugh A
HA
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
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