Virus-Like Particle Based Immunization Against Peanut Allergy

基于病毒样颗粒的花生过敏免疫研究 项目摘要 食物过敏是由不平衡的免疫反应引起的，免疫反应导致IgE的产生， 以IgE依赖性方式异常激活粒细胞和相关细胞。花生过敏是最 严重的这些条件，影响超过2%的儿童在美国与潜在的严重 后果口服免疫疗法标准治疗在有效时仅提供暂时缓解， 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IgG抗体，表明产生特异性、高亲和力 记忆反应可以包括针对食物过敏的直接和持久的治疗。这个程序 结合了基于蛋白质的免疫原设计和生产经验丰富的实验室的技能， 纳米颗粒与领先的研究人员在研究和治疗食物过敏。该研究将探索 一种亚单位疫苗策略，其中过敏性和非过敏性肽来源于两个重要的花生 过敏原Ara h 2和Ara h 6存在于孔中免疫原性病毒样颗粒的表面上， 控制和良好的特点的方式。这些候选疫苗的反应将与 配方纳入全长蛋白质，最好的候选人将先进的过敏试验 在两种小鼠模型中的抑制。第一种是由以下物质诱导的变态反应和过敏反应的标准模型： 第一种是给予过敏原和霍乱毒素作为佐剂，第二种是新的小鼠品系， 表现出更临床相关的表型，其中过敏是由口服过敏原引起的 没有佐剂。如果免疫反应确实能够集中在特定的过敏原序列上， 将能够确定最小化的一组IgG应答是否可以诱导显著的保护， 开发有效的组合，达到预期的目标，副作用最小。

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.