Safe and rapid suppression of food allergy by a suppressive B cell response
Food allergy, the most common cause of anaphylaxis, is responsible for approximately 150 deaths a year in the U.S. Severe food allergy is mediated by allergen-specific IgE that triggers histamine and other mediator release by mast cells. Subsequently, this leads to increased vascular and intestinal permeability and consequently to shock and diarrhea. Disease can be suppressed in mice and in humans by immunization protocols that stimulate protective Tregs and the production of IgG antibodies that activate the inhibitory receptor, FcgammaRIIB, and neutralize absorbed antigen before it can bind to mast cell-associated IgE. However, existing protocols require frequent treatment with increasing allergen doses; this takes months and is ineffective in a considerable proportion of treated individuals. Rapid allergen immunization would be much more effective at blocking food allergy-associated anaphylaxis, but would normally be associated with a high risk for development of anaphylaxis at the time of immunization.
Here, we aim to establish protocols for the safe and rapid induction of a long-lasting food allergy-suppressive immune response, study the underlying mechanisms of antibody-mediated tolerance induction and protection from anaphylaxis and investigate the underlying mechanisms of IL-2 complex-mediated tolerance induction and protection from anaphylaxis.