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年前由Jenner和 巴斯德在100年前从概念上巩固了这一概念，以及程序 仍然会带来惊喜。其中最新的是DNA疫苗接种。一个 T细胞受体的特定可变区基因Vbeta8.2是 重排及其产物在致病T细胞上表达 实验性自身免疫性脑脊髓炎(EAE)及其产品 诱导实验性自身免疫的致病T细胞上的表达 髓鞘免疫H-2/u小鼠后的脑脊髓炎(EAE) 碱性蛋白(MBP)。裸DNA疫苗接种H-2/u小鼠的实验研究 MBP分子的一部分，在接种疫苗的小鼠中表明有一个 将自身免疫反应从Th2逆转为Th2。这种转变可能会使 这一途径对近期Th1介导的白血病的治疗具有吸引力 多发性硬化症、青少年糖尿病和类风湿等疾病 关节炎。我们最近将这种方法扩展到治疗 自身免疫性疾病的多肽配体改变。在本部分中， 计划项目建议，我们的目标是： 1.拓展TCR-VB DNA疫苗免疫机制的研究 构建能诱导Th2反应并抑制EAE。 2.用编码髓鞘表位的DNA微抗原进行免疫试验 以多肽和APL为基础的EAE治疗。 3.研究产生γ-干扰素和IL-1的细菌CpG序列 12，以及它们在抑制EAE方面的应用。 4.利用DNA疫苗免疫趋化因子治疗EAE。 5.开发串联的细胞因子和趋化因子构建物用于治疗EAE。