Food allergy affects approximately 11 million Americans and is escalating in prevalence. There are currently no available treatments and affected individuals are dependent on strict elimination diets and epinephrine to prevent the life-threatening reactions if accidental exposure occurs. Very little is known about the mechanisms that underlie the incidence, severity and spectrum of responses seen in food allergic patients. A significant reason for this has been the lack of an animal model that recapitulates the physiological and immunological features of food allergy. Previously utilized models are severely limited to specific strains of mice, large antigen doses or nonphysiological routes of immunization and have failed to elicit the hallmark immunological responses. We have developed a novel model using commonly used inbred mouse strains, antigen doses that are comparable to dietary levels and exposure via ingestion. Our model uses administration of food antigens (egg and peanut) concurrently with low amounts of Staphylococcus aureus enterotoxin B (SEB), a common food contaminant. This elicits immunological and physiological responses that mirror food allergic patients and represents a significant advance from other models. This proposal centers upon improving food allergy research in three directions: optimization of our model (Aim 1), development of state-of-the-art physiological monitoring (Aim 2) and potential application to screening therapeutics (Aim 3).
There aims are:
Aim 1 : Establish the threshold levels of sensitizing antigen, SEB and challenging antigen doses.
Aim 2 : Develop methodology that will allow standardized, investigator independent, methods for monitoring physiological responses in our food allergy model.
Aim 3 : Test the effectiveness of a highly novel, bispecific antibody that inhibits IgE-mediated allergic responses in preventing anaphylaxis to peanut. We believe that these aims will facilitate our abilities to investigate the pathogenesis and immunological mechanisms underlying this disease and prove a novel, important tool for developing future therapies and clinical treatments.
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