Prevention and treatment of food allergy by specific glycation and peptide-based oral immunotherapy

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The prevalence of food allergies varies across countries and it ranges 4-8% in children and 1-5% in adults in North America. Earliest allergy cases (onset before the age of 6 months) involve mainly cow's milk and then allergies to egg (2nd most common food allergen). There is currently no treatment for food allergy. However, in children, tolerance can be naturally achieved and some allergies may diminish or disappear with age. The two-third of egg allergy children acquire tolerance at the age of 5 years, however, 35% of children remain allergic throughout their lives. In the previous work, we demonstrated genetically engineered ovomucoid (OVM) (one of major egg allergens) by means of site-directed mutagenesis and glycosylation can modulate allergic responses and induce tolerance in egg allergy mouse model. Furthermore, we reported that orally administered synthetic ovalbumin (OVA) multiple T-cell epitopes can suppress allergic responses in an egg allergy mouse by the elicitation of FoxP3 and TGF-beta associated mechanisms. These glycation and peptide-based immunotherapy represents an attractive approach for targeting interventions in food allergy. In this view, we further study systematic induction of mucosal tolerance of egg allergy using various types of glycation forms of OVA (glucose, D-mannose, glucomannan, , and galactomannan) and peptides derived from OVM depleted heat denatured egg white proteins. Ex-vivo study on antigen uptake and presentation by dendritic cells will be performed. An established egg allergy Balb/c model will be used in vivo study. Gastrointestinal (GI) mucosal immune responses will be characterized by analyzing various biomarkers of serum histamine, specific IgE, IgG, various cytokine secretion, GI local gene expression and CD4 cell analysis. Particularly, Th1, Th2, Th17 and T reg cells and toll like receptor functions are main target in this study. We will examine the mechanism of oral tolerance induction and explore novel immunotherapeutic strategies for treatment and prevention of food allergy.