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.

该项目旨在开发新颖的免疫学 过敏性疾病以及实验室技术的疗法 需要了解他们的行动和理性机制 应用。我们已经开发了高度敏感的过敏原特异性 T细胞细胞因子测定法，使我们直接通过POT 在过敏原临床试验中检查细胞因子反应的方法 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以及 提供有关行动机制的见解 免疫调节疗法。正在追求的策略 包括在过敏原中给予RHIL-12作为佐剂 免疫疗法以及研究 传统的免疫疗法。我们正在应用类似的方法 小鼠疫苗模型以了解DNA疫苗如何产生 特定的免疫反应。迄今为止，我们已经开发了一种抗原 利用细胞仪的特定测定法，允许直接检测 单细胞水平的复杂细胞因子表型。我们有 检查了对空气过敏剂（例如房屋）的细胞因子反应 灰尘，螨虫和猫，在 过敏性哮喘患者，但在健康中几乎无法检测到的反应 控件。这些结果表明，正常T细胞对 无处不在的航空过敏剂是耐受性。使用RHIL-12的I期试验 作为过敏原免疫疗法中的辅助药已被 Niaid，IRB，正在等待FDA批准。抗原特异性 细胞因子流量已应用于小鼠的DNA疫苗接种， 证明DNA疫苗接种产生了持久的TH1 CD4+和CD8+子集的极化免疫反应， 而蛋白质免疫会产生更瞬时的反应 限于CD4 T细胞。