DNA VACCINATION AS EAE IMMUNOTHERAPY

DNA 疫苗接种作为 EAE 免疫疗法

• 批准号: 6485959
• 负责人: LAWRENCE STEINMAN
• 金额: $ 19.62万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6485959
• 关键词: T cell receptor; autoimmunity; chemokine; disease /disorder model; experimental allergic encephalomyelitis; gene therapy; immune tolerance /unresponsiveness; immunotherapy; interferon gamma; interleukin 10; interleukin 12; interleukin 4; laboratory mouse; laboratory rat; multiple sclerosis; myelin basic proteins; polymerase chain reaction; transfection /expression vector; vaccine development; vector vaccine

Vaccination was initiated empirically 200 years ago by Jenner and consolidated conceptually 100 years ago by Pasteur, and the procedure still provides surprises. Among the latest is vaccination with DNA. A particular variable region gene of the T cell receptor, Vbeta8.2, is rearranged and its product is expressed on pathogenic T cells that induce experimental autoimmune encephalomyelitis (EAE) and its product is expressed on pathogenic T cells that induce experimental autoimmune encephalomyelitis (EAE) in H-2/u mice following immunization with myelin basic protein (MBP). Vaccination of H-2/u mice with naked DNA pathogenic portion of the MBP molecule, indicated in the vaccinated mice there was a reversal of the autoimmune response from Th2 to Th2. This shift may make this approach attractive for treatment of recently of Th1 mediated diseases like multiple sclerosis, juvenile diabetes, and rheumatoid arthritis. We have recently extended this approach to the treatment of autoimmune diseases with altered peptide ligands. In this portion of the program project proposal, we aim to: 1. Extend studies on the mechanism whereby DNA vaccination with TCR Vb constructs induces Th2 responses and suppresses EAE. 2. Test vaccination with DNA minigens encoding myelin epitopes for peptide- and APL-based treatment of EAE. 3. Investigate bacterial CpG sequences inducing gamma interferon and IL- 12, and their application for suppression of EAE. 4. Utilize DNA vaccination to chemokines for treatment of EAE. 5. Develop tandem cytokine and chemokine constructs for treatment of EAE.

疫苗接种是200年前詹纳（Jenner）和 100年前的概念上合并了巴斯德的概念，该程序 仍然提供惊喜。最新的是DNA疫苗接种。一个 T细胞受体的特定变量区域基因VBETA8.2为 重新排列及其产物在诱导的致病性T细胞上表达 实验性自身免疫性脑脊髓炎（EAE）及其产物是 在诱导实验性自身免疫性的致病性T细胞上表达 髓磷脂免疫后，H-2/U小鼠的脑脊髓炎（EAE） 碱性蛋白质（MBP）。裸体DNA致病性的H-2/U小鼠疫苗接种 在接种小鼠中指示的MBP分子的一部分 自身免疫反应从Th2逆转到Th2。这种转变可能会导致 这种方法可吸引最近Th1介导的治疗 诸如多发性硬化症，青少年糖尿病和类风湿病等疾病 关节炎。我们最近将这种方法扩展到了 肽配体改变的自身免疫性疾病。在这部分 计划项目建议，我们的目标是： 1。扩展对使用TCR VB接种DNA疫苗的机制的研究 构造诱导Th2响应并抑制EAE。 2。用编码髓磷脂表位的DNA疫苗接种 EAE的肽和基于APL的治疗。 3。研究诱导伽马干扰素和IL-的细菌CpG序列 12，以及他们抑制EAE的应用。 4。利用DNA疫苗接种趋化因子来治疗EAE。 5。开发串联细胞因子和趋化因子构建体以治疗EAE。