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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

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.[1]

References

  1. Persistent protective effect of heat-killed Escherichia coli producing "engineered," recombinant peanut proteins in a murine model of peanut allergy. Li, X.M., Srivastava, K., Grishin, A., Huang, C.K., Schofield, B., Burks, W., Sampson, H.A. J. Allergy Clin. Immunol. (2003) [Pubmed]
 
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