(9c) Nanoallergens: A Nanoparticle Platform for Identifying Crucial Allergy Epitopes

Allergy is a disorder of the immune system which is elicited by the allergen-mediated-clustering of the immunoglobulin E (IgE) molecules on the surface of mast cells and basophils. Allergenic diseases are a major cause of illness and disability in the US, and there is broad consensus that the prevalence of type I allergy is increasing worldwide. The majority of the current therapies used to treat allergy related adverse immunologic responses involve non-specific suppression of parts of the immune system. More targeted therapies would improve the effectiveness of allergy treatment, but would also require a more thorough assessment of antigenic regions (also known as epitopes) on allergen proteins.  During allergic reactions, allergen specific IgE molecules bind multivalently to an allergen protein, causing the release of inflammatory cytokines.  A possible allergy inhibitor design would be a mimetic of these IgE binding epitopes, which competitively block IgEs from binding allergen proteins, thus preventing allergic reactions.  Therefore, we have engineered a new method for determining the most antigenic (allergic reaction inducing) epitopes on allergens using allergen mimetics we call nanoallergens.  Nanoallergens are liposomal nanoparticles that have been modified to display linear peptide as epitope mimetics in a multivalent fashion and trigger allergic reactions.  Using a method developed in our laboratory, we can synthesize nanoallergens to display several epitope peptides, allowing us to systematically determine a single allergen epitope’s contribution to the overall antigenicity of an allergen protein.  Using nanoallergens, we demonstrate the importance of a single highly antigenic allergy epitope in the major peanut allergen ara h 2.  We also present several other, lower antigenic epitopes that are important for overall degranulation response, which are vastly underestimated by more conventional epitope characterization techniques.  This novel method is a versatile tool that can be used for any allergen and will likely provide important information for future inhibitor design.