Developmental Immunotherapeutics for Allergic Diseases and Asthma

过敏性疾病和哮喘的发育免疫治疗

• 批准号: 6099081
• 负责人: Dean D Metcalfe
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6099081
• 关键词: T lymphocyte; airborne allergen; asthma; biological models; cellular immunity; clinical research; cytokine; flow cytometry; human subject; hypersensitivity; immunologic assay /test; immunomodulators; immunotherapy; interleukin 12; laboratory mouse; model design /development; vaccine development; vector vaccine

This project seeks to develop novel immunologic therapies for allergic diseases as well as the Laboratory techniques required to understand their mechanism of action and rational application. We have developed a highly sensitive allergen specific T cell cytokine assay which allows us a direct high through put means to examine cytokine responses in clinical trials of allergen immunotherapy. This technique directly measures both the frequency and cytokine profile of antigen specific T cells and provides insight into the mechanism of action of immunomodulatory therapies. Strategies that are being pursued include the administration of rhIL-12 as an adjuvant in allergen immunotherapy as well as studies of the mechanisms of action of traditional immunotherapy. We are applying a similar approach to mouse vaccine models to understand how DNA vaccines generate specific immune responses. To date, we have developed an antigen specific assay utilizing cytometry, allowing the direct detection of complex cytokine phenotypes at the single cell level. We have examined the cytokine response to aeroallergens such as house dust, mite and cat, demonstrating a uniform Th2 response in allergic asthmatics but little or not detectable response in healthy controls. These results suggest that the normal T cell response to ubiquitous aeroallergens is tolerance. A phase I trial using rhIL-12 as an adjuvant in allergen immunotherapy has been approved by the NIAID, IRB and is waiting FDA approval. Antigen specific cytokine flow has been applied to DNA vaccination of mice, demonstrating that DNA vaccination creates a long lasting Th1 polarized immune response in both CD4+ and CD8+ subsets, whereas protein immunization generates a more transient response limited to CD4 T cells.

该项目旨在开发新的免疫学 过敏性疾病的治疗以及实验室技术 需要了解其作用机制和合理的 应用程序.我们研制了一种高敏感性的过敏原特异性 T细胞细胞因子测定，它使我们能够直接高通量 在过敏原临床试验中检查细胞因子应答的方法 免疫疗法该技术直接测量 抗原特异性T细胞的频率和细胞因子谱， 提供了深入了解的作用机制， 免疫调节疗法。正在执行的战略 包括给予rhIL-12作为过敏原中的佐剂 免疫疗法以及研究的作用机制， 传统免疫疗法我们正在采用类似的方法， 小鼠疫苗模型，以了解DNA疫苗如何产生 特异性免疫反应。到目前为止，我们已经开发出一种抗原 利用细胞计数的特异性测定，允许直接检测 复杂的细胞因子表型在单细胞水平。我们有 检查了细胞因子对空气过敏原的反应， 灰尘，螨和猫，表现出一致的Th 2反应， 过敏性哮喘，但很少或检测不到反应，在健康 对照这些结果表明，正常的T细胞反应， 普遍存在的空气过敏原是耐受性。使用rhIL-12的I期试验 作为过敏原免疫疗法中的佐剂， NIAID、IRB和正在等待FDA批准。抗原特异性 细胞因子流已经应用于小鼠的DNA接种， 证明DNA疫苗可以产生一个持久的Th 1， 在CD 4+和CD 8+亚群中的极化免疫应答， 而蛋白质免疫产生的反应更短暂 仅限于CD 4 T细胞。