(191cj) A Novel Diagnostic Liposomal Platform, Nanoallergen, for Clinical Evaluation of Epitope Immunogenicity of Peanut Allergen

Authors: 
Kim, B., University of Notre Dame
Deak, P., University of Notre Dame
Shin, J., University of Notre Dame
Vrabel, M., University of Notre Dame
Kiziltepe, T., University of Notre Dame
Bilgicer, B., University of Notre Dame
Currently, several diagnostics have been developed for diagnosis of allergies such as Skin Prick Test (SPT) and ImmunoCAP specific IgE blood test. Although the existing diagnostics are able to determine whether patients are allergic to a suspected allergen, they are unable to determine the effect of specific epitopes present on allergen proteins on physiological allergic responses, leading to a high likelihood of inaccurate predictions of physiological allergy symptoms for patients. Since it has been shown that severe allergic symptoms are correlated with certain immunogenic epitopes, it is important to evaluate individual epitope immunogenicity for predictions of severe clinical allergic responses. In this regard, we developed a liposomal-based platform we call nanoallergens to evaluate epitope immunogenicity of the suspected allergen so as to determine which immunogenic epitopes play a critical role in severe allergic responses. Nanoallergens are a liposomal synthetic allergen that multivalently displays potential IgE binding epitopes of the allergen proteins. As experimental approaches, we synthesized IgE binding epitope mimetics derived from the major peanut allergen protein (Ara h 2) with a lipid conjugate, loaded them on the nanoallergen platform, and performed in vitro RBL cellular degranulation assays to evaluate epitope immunogenicity of the Ara h 2 protein for triggering degranulation responses using clinical samples of highly allergic patients. The nanoallergen study showed that certain immunogenic epitopes induced strong degranulation responses for the tested patient sera with clinical history of severe allergic symptoms, suggesting that nanoallergens allow for predictions of severe allergic reactions by correlating between immunogenic epitopes and severe allergic reactions. Furthermore, we performed basophil activation tests using clinical samples of a large population of severe allergic subjects to investigate whether the evaluated immunogenic epitopes by nanoallergen study are critical for severe physiological responses of peanut allergy patients. In conclusion, nanoallergens could potentially be used as a diagnostic tool for predictions of severe peanut allergic responses.
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