Abstract
Current methods for detection and diagnosis of allergies do not provide epitope specific immunogenic information and hence lack critical information that could aid in the prediction of clinical responses. To address this issue, we developed a nanoparticle based platform, called nanoallergens that enable multivalent display of potential allergy epitopes for determining the immunogenicity of each IgE binding epitope. By synthesizing nanoallergens that present various epitopes from the major peanut allergen, Ara h2, we directly determined the immunogenicity of each epitope, alone and in combination with other epitopes, using patient sera. This information provided insights on which epitopes are most critical for physiological responses to Ara h2 and revealed the importance of both high and low affinity epitopes for allergic responses. We anticipate the nanoallergen platform to be used to provide information regarding allergic reactions and therefore potentially aid in more accurate diagnosis and design of personalized treatment options.
Highlights
We chose a combination of two different epitopes, a highly immunogenic one and a low immunogenic one based on our results shown in Fig. 4, to observe the impact of low immunogenic epitopes when presented in combination with highly immunogenic epitopes
One of the key findings of this study is that nanoallergens that displayed a combination of high and low immunogenic epitopes can trigger more degranulation at a hundred-fold lower concentration than the nanoallergen displaying high immunogenic epitope alone for one of the patient samples, despite the reduction in the density of the high immunogenic epitope on particle surface
Avidity of a multivalent entity depends on both the monovalent affinities of the moieties as well as the total number of binding interactions, the valency of the epitopes on nanoallergens as well as of the IgEs on cell surface carry significance. Immunogenicity depends upon both EC50 and Degranulation maximum (Dmax), the inclusion of low affinity epitopes can improve the overall avidity of the nanoallergen-IgE/FcεRI interaction by providing additional anchorage points for binding, thereby decreasing the EC50
Summary
The goal of this study is to establish nanoallergens as a versatile platform to study the immunogenicity of potential IgE binding epitopes of major allergen proteins
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