Virus-Like Particle Based Immunization Against Peanut Allergy

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Virus-Like Particle Based Immunization Against Peanut Allergy PROJECT SUMMARY Food allergies result from unbalanced immune responses that result in the production of IgE and the aberrant activation of granulocytes and related cells in an IgE-dependent manner. Peanut allergy is the most serious of these conditions, affecting more than 2% of children in the U.S. with potentially severe consequences. The oral immunotherapy standard of care provides only temporary relief when effective, and frequently gives rise to serious side effects. Its effectiveness is associated with the production of antigen- specific IgG antibodies, suggesting that an immunization protocol which gives rise to a specific, high-affinity memory response may comprise a direct and long-lasting therapy against food allergy. This program combines the skills of a laboratory experienced in the design and production of immunogens based on protein nanoparticles with leading investigators in the study and treatment of food allergy. The research will explore a subunit vaccine strategy in which allergenic and non-allergenic peptides derived from two important peanut allergens, Ara h 2 and Ara h 6, are presented on the surface of immunogenic virus-like particles in a well- controlled and well-characterized manner. The response to these candidate vaccines will be compared to formulations incorporating the full-length proteins, and the best candidates will be advanced to tests of allergy inhibition in two mouse models. The first is a standard model of allergy and anaphylaxis induced by administration of the allergen and cholera toxin as an adjuvant, and the second is a new mouse strain that exhibits a more clinically relevant phenotype in which allergy is induced by oral consumption of the allergen without adjuvant. If the immune response is indeed able to be focused on specific allergenic sequences, one would be able to determine if a minimized set of IgG responses can induce significant protection and to develop effective combinations that achieve the desired goal with a minimum of side effects.