Experimental Therapy for Peanut Allergy with Novel Peanut-Human Fusion Prote

新型花生-人类融合蛋白治疗花生过敏的实验疗法

• 批准号: 7894028
• 负责人: Daocheng Zhu
• 金额: $ 22.88万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7894028
• 关键词: Address; Affinity; Allergen Immunotherapy; Allergens; Allergic; Allergic Disease; Allergic Reaction; Allergic inflammation; Allergy to peanuts; Anaphylaxis; Antigens; Arts; Basophils; Binding; Chimeric Proteins; Epinephrine; Food; Food Hypersensitivity; Goals; Health; Human; Hypersensitivity; IgE; IgE Receptors; Immune response; Immunotherapy; Incidence; Inhalant dose form; Intervention; Investigational Therapies; Lead; Life; Link; Long-Term Effects; Mediating; Mediator of activation protein; Modeling; Mus; Oral; Peanuts - dietary; Phase; Plants; Play; Proteins; Reaction; Recombinants; Role; Series; Testing; Therapeutic; Therapeutic Index; Work; allergic response; desensitization; effective therapy; food allergen; in vivo; mast cell; mouse model; novel; research study; response; subcutaneous

DESCRIPTION (provided by applicant): Food allergy is a serious health problem with increasing incidence. Peanut is one of the most life threatening allergenic foods. In contrast to allergic disease due to inhalant allergens, there are no effective treatments other than strict avoidance and rapid intervention with epinephrine when reactions do occur. Peanut-induced allergic reactions are mediated by antigen-specific IgE bound to the high-affinity receptor for IgE (Fc RI) on mast cells and basophils. Mast cells and basophils play critical roles in allergic inflammation. The long-term objective of this proposal is to develop a new form of peanut-human fusion protein for treatment of peanut- induced allergy. Here we hypothesize that peanut allergen-Fc fusion protein may block peanut-induced allergic reaction and serve as allergen immunotherapy to induce a protective immune response. To achieve this goal, we will test the ability of peanut-human fusion protein to acutely inhibit peanut-induced allergic response in a peanut-induced allergic mouse model that consists of both early and late phase responses to oral challenge with peanut. To test a long term effect induced by the allergen-gamma fusion protein, we plan to develop a peanut allergen-mouse Fc 2a fusion protein. We will explore the mechanism of allergen-gamma fusion protein-induced immune responses in vivo. We will determine whether the allergen-mouse Fc protein induces a protective immune response in mice. We will also treat mice with allergen-gamma fusion protein and determine if mice treated with allergen-gamma fusion protein will be protected from challenge with complete peanut extract. If these experiments work as projected, this approach may lead the way to the first effective therapy for humans with severe allergy to peanut. This proposal is directed toward developing a therapeutic strategy for peanut allergy by using a recombinant peanut-human fusion protein. This molecule will be allergen specific and may provide a new platform for allergen immunotherapy of food allergy.

描述（由申请人提供）：食物过敏是发生率增加的严重健康问题。花生是最威胁人生的过敏性食物之一。与由于吸入过敏原引起的过敏性疾病相反，除了严格的避免和对肾上腺素的快速干预外，没有其他有效的治疗方法。花生诱导的过敏反应是由与肥大细胞和嗜碱性粒细胞上IgE（FC RI）结合的抗原特异性IgE介导的。肥大细胞和嗜碱性物质在过敏性炎症中起关键作用。该提案的长期目标是开发一种新形式的花生 - 人类融合蛋白来治疗花生诱导的过敏。在这里，我们假设花生过敏蛋白-FC融合蛋白可能会阻止花生诱导的过敏反应，并用作过敏原免疫疗法，以诱导保护性免疫反应。为了实现这一目标，我们将测试花生 - 人类融合蛋白急性抑制花生诱导的过敏反应的能力，该反应在花生诱导的过敏小鼠模型中包括早期和晚期对花生口腔挑战的反应。为了测试过敏原融合蛋白引起的长期作用，我们计划开发花生过敏蛋白鼠标FC 2A融合蛋白。我们将探索过敏原融合蛋白诱导的体内免疫反应的机制。我们将确定过敏原的FC蛋白是否诱导小鼠的保护性免疫反应。我们还将用过敏蛋白融合蛋白治疗小鼠，并确定用过敏蛋白 - γ融合蛋白治疗的小鼠是否会受到完全花生提取物的挑战。如果这些实验可以按预期的方式工作，则这种方法可能会导致对对花生过敏的人类的首次有效疗法。 该提案用于使用重组花生 - 人类融合蛋白来制定花生过敏的治疗策略。该分子将是过敏原特异性的，可以为食物过敏的过敏原免疫疗法提供新的平台。