A novel murine model of food allergy to peanut or egg

对花生或鸡蛋食物过敏的新型小鼠模型

• 批准号: 7451159
• 负责人: PAUL J BRYCE
• 金额: $ 22.04万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7451159
• 关键词: Accident and Emergency department; Acids; Adult; Affect; Allergic; Allergy to peanuts; American; Anaphylaxis; Animal Model; Antigens; Arts; Asthma; Atopic Dermatitis; Bispecific Antibodies; Cessation of life; Characteristics; Child; Childhood; Class; Clinical Treatment; Condition; Data; Development; Diet; Disease; Dose; Eczema; Effectiveness; Enterotoxins; Epinephrine; Family member; Fishes; Flare; Food; Food Contamination; Food Hypersensitivity; Future; Gastroenteritis; Generations; Health Expenditures; Hypersensitivity; IgE; Immune response; Immunization; Immunoglobulins; Inbred Strains Mice; Incidence; Individual; Inflammation; Ingestion; Injectable; Insulin-Dependent Diabetes Mellitus; Left; Life; Light; Meat; Mediating; Methodology; Methods; Milk; Modeling; Molecular; Mouse Strains; Mus; Oral Administration; Organism; Ovalbumin; Patch Tests; Pathogenesis; Patients; Peanuts - dietary; Physiologic Monitoring; Physiological; Prevalence; Process; Proteins; Psoriasis; Quality of life; Rate; Reaction; Research; Research Personnel; Resistance; Rhinitis; Risk Factors; Route; Screening procedure; Severities; Shellfish; Site; Skin; Social Interaction; Staphylococcus aureus; Statistically Significant; Stomach; Testing; Therapeutic; Therapeutic Intervention; Toxin; United States; Visit; antigen challenge; egg; food allergen; improved; inhibiting antibody; innovation; novel; prevent; response; sensitizing antigen; tool

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.

描述（由申请人提供）：食物过敏影响大约1100万美国人，并且患病率正在上升。目前没有可用的治疗方法，受影响的个体依赖于严格的消除饮食和肾上腺素，以防止发生意外暴露时危及生命的反应。关于食物过敏患者中观察到的反应的发生率、严重程度和谱的机制知之甚少。一个重要的原因是缺乏一个动物模型，概括的生理和免疫学特征的食物过敏。以前使用的模型严重限于特定品系的小鼠、大抗原剂量或非生理免疫途径，并且未能引起标志性免疫应答。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， 与膳食水平和通过摄入的接触量相当。我们的模型使用的食物抗原（鸡蛋和花生）的管理，同时低量的金黄色葡萄球菌肠毒素B（SE B），一种常见的食品污染物。这激发了反映食物过敏患者的免疫和生理反应，代表了其他模型的重大进步。该提案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）和潜在的应用筛选疗法（目标3）。目的1：建立致敏抗原、SEB和攻击抗原剂量的阈值水平。目标二：开发方法学，允许标准化，独立于研究者的方法，用于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反应。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机制，并证明是开发未来疗法和临床治疗的一种新的重要工具。