LIT, a rapid, safe, and effective liver-targeted allergen immunotherapy to prevent anaphylaxis in food sensitized subjects 2504

Abstract Description Food allergies affect up to 10% of the U.S. population and their prevalence have risen over the last decade. Allergen immunotherapy (AIT) holds the promise for durable disease control by establishing allergen-specific tolerance through repeated introduction of native allergens. However, its efficacy can be limited by long interventions, reactions upon administration, and poor patient compliance. We previously introduced LIT, a novel liver-targeted AIT that harnessed the liver’s intrinsic tolerance-inducing mechanisms to induce allergen-specific regulatory T cells (Treg) and treat allergic airway disease. Here, LIT protects sensitized subjects from anaphylaxis-induced death in a pre-clinical model of food allergy. Our data demonstrate that LIT is well-tolerated in sensitized mice and promotes an increase in Tregs, selectively expanding T follicular regulatory cells. Furthermore, LIT-treated mice exhibited a reduction in IL-13 producing T follicular helper cells (TFH13), which facilitate the development of anaphylactic IgE. The reduction in TFH13 correlated with reduced, allergen-specific, germinal center and IgE+ B cells, as well as reduced clinical and serological features of anaphylaxis. Taken together, our data serve as a proof-of-concept study by which LIT can ameliorate clinical features of food allergies and prevent death from anaphylaxis. Funding Sources Supported by the Chicago Immunoengineering Innovation Center and the Alper fund. Topic Categories Vaccines and Immunotherapy (VAC)