Virus-Like Particle Based Immunization Against Peanut Allergy

花生过敏病毒样颗粒免疫研究 项目总结 食物过敏是由于免疫反应不平衡导致免疫球蛋白E和 粒细胞及相关细胞以IgE依赖的方式异常激活。花生过敏是最严重的 这些疾病的严重性，影响了美国超过2%的儿童，可能患有严重的 后果。口服免疫疗法的护理标准在有效时只提供暂时的缓解，并且 经常会引起严重的副作用。它的有效性与抗原的产生有关- 特异性的免疫球蛋白抗体，表明一种免疫方案能产生一种特定的、高亲和力的 记忆反应可能包括针对食物过敏的直接和持久的治疗。本节目 结合了实验室在设计和生产基于蛋白质的免疫原方面的经验 纳米粒子与领先的研究人员一起研究和治疗食物过敏。这项研究将探索 一种亚单位疫苗策略，其中过敏性和非过敏性多肽来自两个重要的花生 过敏原Ara h 2和Ara h 6存在于井中免疫原性病毒样颗粒的表面- 有节制的，有特点的。对这些候选疫苗的反应将与 含有全长蛋白质的配方和最佳候选者将进入过敏测试 两种小鼠模型的抑制作用。第一种是标准的过敏症和过敏反应模型。 注射过敏原和霍乱毒素作为佐剂，第二种是一种新的小鼠品系， 表现出一种临床上更相关的表型，即由口服过敏原引起的过敏 不加佐剂。如果免疫反应确实能够集中在特定的致敏序列上，那么 能够确定最小化的一组免疫球蛋白应答是否可以产生显著的保护作用，并 开发有效的组合，以最小的副作用实现预期目标。

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.