Allergen loaded nanoparticles for food allergy tolerance

This proposal is a continuation of the long-standing collaboration between the Shea and Miller Laboratories examining tolerogenic therapy in Th1/17-mediated autoimmune diseases. The personnel in my laboratory listed in the budget justification will carry out the in vivo mechanistic experiments detailed in Aims 1 and 2 determining the the efficiency of tolerance of PLG particle formulations identified by Dr. Shea’s laboratory for their ability to prevent and treat ongoing Th2-mediated models of food allergy induced by immunization with either peanut (PN) or egg albumin (OVA) proteins. In addition, my lab will carry out the in vivo and in vitro experiments detailed in Aim 2 examining the mechanisms (deletion, anergy, immune deviation and T cell regulation) by which Th2 tolerance is induced and maintained using Ag-encapsulating PLG nanoparticles (proliferation, ELISPOT, intracellular cytokine staining, etc.), and assays related to quantitation of gut inflammation using flow cytometric analyses of peripheral and gut-infiltrating immune inflammatory cells and staining of frozen gut sections. I will consult regularly with Drs. Shea and O’Konek and their lab personnel at the University of Michigan via regular skype meetings and twice yearly in person meetings to review data and plan experiments, as well as meeting daily with my lab personnel to discuss experimental design and results.