(590a) Engineering Selective Immunoglobulin E Inhibitors for Peanut Allergies

Authors: 
Deak, P., University of Notre Dame
Kim, B., University of Notre Dame
Vrabel, M., University of Notre Dame
Kiziltepe, T., University of Notre Dame
Bilgicer, B., University of Notre Dame
Food allergies are a growing concern in the US; drastic increases in patients who have severe allergies to such common foods as peanuts, tree nuts, milk, eggs, wheat and shellfish are a serious health concern that causes problems for patients, doctors and the food processing industry. This problem is further compounded by the lack of pre-reaction therapeutics; instead, patients can only manage symptoms after allergen exposure. We propose a new twostep, methodology for developing patient-specific therapeutics for food allergies by inhibiting allergen specific immunoglobulin E (IgE) molecules, the molecule primarily responsible for triggering severe allergic reactions. One of the challenges in allergen specific IgE inhibition is the clonal variability and the variety of potential IgE binding epitopes on food allergy proteins. Using our method of inhibitor development, each patient’s serum is screened using nanoallergens, liposomes displaying potential IgE binding epitopes, in order to assess and determine the most immunodominant IgE binding epitopes for each patient. Next, we synthesize specific inhibitions, called covalent heterobivalent inhibitors (cHBIs) using the information gleaned from the nanoallergen assessment. The result is a personalized allergy treatment that can potently inhibit allergen specific IgEs with a combination of bivalent binding to improve specificity and covalent interactions to provide long term inhibition. We have demonstrate the utility of this technique by evaluating four peanut allergy patients’ sera using nanoallergens and subsequently crafting specific cHBIs for the most potent peanut protein epitopes for these patients. This cHBI cocktail showed specific binding only to allergy patient IgEs and ex vivo inhibition of degranulation using a standard cellular assay. This study provides the groundwork for the nanoallergen-cHBI method for developing targeted allergy therapeutics for any food allergy.