A novel murine model of food allergy to peanut or egg

描述(由申请人提供)：食物过敏影响了大约1100万美国人，而且患病率正在上升。目前还没有可用的治疗方法，受影响的个人依赖严格的排泄饮食和肾上腺素来防止意外暴露发生的危及生命的反应。关于食物过敏患者的发病率、严重性和反应频谱的机制，人们知之甚少。这一现象的一个重要原因是缺乏概括食物过敏的生理和免疫学特征的动物模型。以前使用的模型严重局限于特定品系的小鼠、大剂量的抗原或非生理学的免疫途径，未能引起标志性的免疫反应。我们已经开发了一种新的模型，使用常用的近交系小鼠品系，抗原剂量是 与饮食水平和摄入暴露相当。我们的模型同时使用食物抗原(鸡蛋和花生)和低剂量的金黄色葡萄球菌肠毒素B(SEB)，这是一种常见的食物污染物。这引发了反映食物过敏患者的免疫和生理反应，与其他模型相比，这是一个重大进步。这项建议集中在三个方向上改进食物过敏研究：优化我们的模型(目标1)，发展最先进的生理监测(目标2)和潜在的应用于筛查疗法(目标3)。目标1：确定致敏抗原、SEB和挑战抗原剂量的阈值水平。目标2：开发方法学，允许标准化的、独立于研究者的方法来监测我们的食物过敏模型中的生理反应。 目的3：测试一种高度新颖的双特异性抗体抑制IgE介导的过敏反应的有效性 预防花生过敏反应的效果。我们相信，这些目标将有助于我们研究这种疾病的发病机制和免疫学机制，并为未来的治疗和临床治疗提供一个新的、重要的工具。

DESCRIPTION (provided by applicant): Food allergy affects approximately 11 million Americans and is escalating in prevalence. There are currently no available treatments and affected individuals are dependent on strict elimination diets and epinephrine to prevent the life-threatening reactions if accidental exposure occurs. Very little is known about the mechanisms that underlie the incidence, severity and spectrum of responses seen in food allergic patients. A significant reason for this has been the lack of an animal model that recapitulates the physiological and immunological features of food allergy. Previously utilized models are severely limited to specific strains of mice, large antigen doses or nonphysiological routes of immunization and have failed to elicit the hallmark immunological responses. We have developed a novel model using commonly used inbred mouse strains, antigen doses that are comparable to dietary levels and exposure via ingestion. Our model uses administration of food antigens (egg and peanut) concurrently with low amounts of Staphylococcus aureus enterotoxin B (SEB), a common food contaminant. This elicits immunological and physiological responses that mirror food allergic patients and represents a significant advance from other models. This proposal centers upon improving food allergy research in three directions: optimization of our model (Aim 1), development of state-of-the-art physiological monitoring (Aim 2) and potential application to screening therapeutics (Aim 3). There aims are: Aim 1: Establish the threshold levels of sensitizing antigen, SEB and challenging antigen doses. Aim 2: Develop methodology that will allow standardized, investigator independent, methods for monitoring physiological responses in our food allergy model. Aim 3: Test the effectiveness of a highly novel, bispecific antibody that inhibits IgE-mediated allergic responses in preventing anaphylaxis to peanut. We believe that these aims will facilitate our abilities to investigate the pathogenesis and immunological mechanisms underlying this disease and prove a novel, important tool for developing future therapies and clinical treatments.