Persistent protective effect of heat-killed Escherichia coliproducing “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 coliproducing 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) μg 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-γ and TGF-β 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 TH2 and increased TH1 and T regulatory cytokine production. (J Allergy Clin Immunol 2003;112:159-67.)