Immunomodulation of Food Allergy by DNA Based Immunity

Recent studies indicate that food allergy is the leading cause of anaphylaxis treated in American hospital emergency departments, and it is estimated that about 100 deaths occur each year in the US due to food-induced anaphylaxis. Peanut allergy accounts for the majority of these severe anaphylactic reactions. Given the lifelong nature of peanut allergy, these findings highlight the need for novel and effective therapeutic strategies. DNA-based immunization has been an attractive approach in altering the host immune response to antigen (Ag). Recently, the efficacy of intramuscular DNA-based immunization approach in the suppression of IgE synthesis and Th2- associated immune responses has been suggested. The proposed study is directly aimed at determining the immunologic basis of gene immunization, and exploring the utility of this approach in modulating peanut allergen-induced hypersensitivity. The model for this study is hypersensitivity to peanut allergens in an inbred strain of mice (C3H), in which several quantitative parameters of hypersensitivity, including symptom score, the levels of serum specific IgE, plasma histamine, and mast cell degranulation are established. Ara h 2 (17kD) is a major allergen in peanuts, and the T- cell response to Ara h2 appears to be dominant and common in both humans and sensitized C3 mice. In this application, the investigators propose to: (i) generate Ara h2-gene expression constructs, (ii) identify critical Ag-presenting cells; (iii) determine the effects of DNA immunization on peanut allergen-induced IgE synthesis and hypersensitivity, and (iv) examine the modulatory mechanism of DNA-based immunization in peanut hypersensitivity.