DNA VACCINATION AS EAE IMMUNOTHERAPY

DNA 疫苗接种作为 EAE 免疫疗法

• 批准号: 6340678
• 负责人: LAWRENCE STEINMAN
• 金额: $ 18.31万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6340678
• 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年前由詹纳根据经验发起的， 巴斯德在100年前提出了这个概念， 仍然会带来惊喜其中最新的是DNA疫苗。一 T细胞受体的特定可变区基因V β 8.2， 其产物在致病性T细胞上表达， 实验性自身免疫性脑脊髓炎（EAE）及其产物， 在致病性T细胞上表达， 在用髓磷脂免疫后H-2/u小鼠中的脑脊髓炎（EAE 碱性蛋白（MBP）。用致病性裸DNA疫苗接种H-2/u小鼠 MBP分子的一部分，表明在接种疫苗的小鼠中， 自身免疫应答从Th2逆转为Th2。这种转变可能会使 这种方法对于最近治疗Th1介导的 多发性硬化症、青少年糖尿病和类风湿性关节炎等疾病 关节炎我们最近将这种方法扩展到治疗 具有改变的肽配体的自身免疫性疾病。的该部分中 计划项目建议书，我们的目标是： 1. TCRVb DNA疫苗接种机制的扩展研究 构建体诱导Th2应答并抑制EAE。 2.用编码髓磷脂表位的DNA小基因测试疫苗接种， 基于肽和APL的EAE治疗。 3.研究细菌CpG序列诱导γ-干扰素和IL- 12，以及它们用于抑制EAE的应用。 4.利用趋化因子的DNA疫苗治疗EAE。 5.开发用于治疗EAE的串联细胞因子和趋化因子构建体。