Immunobiology of Peanut Allergy and Its Treatment

The prevalence of food allergy has increased over the past 2 decades and food allergy now affects 3.5% to 4% of the U.S. population. Peanut allergy, which is the single leading cause of severe and fatal food-induced allergic reactions in the U.S., affects 1.5 million Americans and has doubled in prevalence in children less than 5 years of age in the period between 1997 and 2002. The reason for this increase in peanut allergy is not known, but it is clear that current strategies for preventing the development of peanut allergy and the severe allergic reactions following accidental ingestion of peanuts are not effective. <P> Preclinical studies from our research group have demonstrated that peanut-allergic mice treated with a novel suppository vaccine, which contained a mixture of engineered, recombinant peanut proteins, Ara h1, 2, and 3, encapsulated within heat-killed E. coli used to generate these proteins (EMP-123), experienced markedly reduced allergic reactions when challenged and had significantly reduced peanut-specific serum IgE and splenocyte Th2 cytokine synthesis in vitro compared to sham-treated mice. <P> The purpose of the proposed Consortium is two-fold: (1) to investigate the natural history of peanut allergy in atopic infants at high risk for the development of peanut allergy, delineate underlying immunologic parameters associated with the natural course of peanut sensitization, and identify biological markers that distinguish young children likely to develop symptomatic peanut allergy; and (2) to test a novel, prototype recombinant modified peanut protein vaccine, EMP-123, for the treatment of peanut allergy. <P> During the Phase I & II clinical trial, immunologic parameters will be followed to delineate the mechanism underlying the response to the vaccine. A third project will utilize our murine model of peanut anaphylaxis and other models to delineate unique properties of the upper and lower Gl tract in establishing tolerance and reversing sensitization, including the role of innate immunity and regulatory cells, and to investigate uptake, processing and immunologic changes induced by EMP-123 in both peanut-sensitized and naive mice. <P> The combined resources of this Consortium provide a unique opportunity to investigate basic immunologic mechanisms associated with the development of oral tolerance or food sensitization, and enable us to test a novel vaccine that has shown great promise in preclinical studies for the treatment of peanut allergy.