CYTOKINE MODULATION OF LENTIVIRAL DNA VACCINES

慢病毒 DNA 疫苗的细胞因子调节

• 批准号: 2555244
• 负责人: WILLIAM P CHEEVERS
• 金额: $ 13.05万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 1999-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2555244
• 关键词: Lentivirus; Retroviridae disease; animal genetic material tag; goats; interferon gamma; interleukin 12; interleukin 4; microorganism culture; microorganism immunology; nonhuman therapy evaluation; plasmids; vaccine development; vector vaccine; virus DNA; virus antigen; virus envelope; virus genetics; virus protein; virus replication

DESCRIPTION (adapted from applicant's abstract): This proposal addresses lentiviral vaccination strategies using the macrophage tropic lentivirus caprine arthritis-encephalitis virus (CAEV), specifically cytokine modulation of Th lymphocyte priming initiated by immunization with plasmid DNA encoding CAEV envelope proteins. The research plan is based on well documented murine studies demonstrating that cross-regulatory cytokines specify the differentiation of Th1 and Th2 lymphocyte subsets at the time of antigen presentation. This principle suggests that antigen specific Th subset responses can be experimentally controlled on an outbred genetic background by cytokine directed priming, a potentially important concept in HIV vaccine design. Thus, the hypothesis to be tested is that expression plasmids encoding caprine interleukin-12 or interferon-gamma will potentiate Thl responses to immunization with CAEV env expression plasmid, whereas plasmid DNA encoding caprine interleukin-4 will potentiate antigen specific Th2 responses. Anticipated results will allow CAEV challenge experiments to evaluate control of lentivirus replication by polarized Thl and Th2 responses to envelope antigens.

描述（改编自申请人摘要）：本提案涉及 使用嗜巨噬细胞慢病毒的慢病毒疫苗接种策略 山羊关节炎-脑炎病毒（CAEV），特别是细胞因子 质粒免疫对Th淋巴细胞启动的调节作用 编码CAEV包膜蛋白的DNA。 该研究计划是基于良好的 有文献记载的鼠类研究表明， 指定Th 1和Th 2淋巴细胞亚群的分化， 抗原呈递 这一原理表明，抗原特异性Th 亚群反应可以通过实验控制在远交遗传上， 背景技术通过细胞因子定向引发， 艾滋病毒疫苗设计。 因此，要检验的假设是， 编码山羊白细胞介素-12或干扰素-γ的质粒将增强 Thl对用CAEV env表达质粒免疫的应答，而 编码山羊白细胞介素-4的质粒DNA将增强抗原特异性 Th 2回应 预期结果将允许CAEV挑战实验， 评价极化Th 1和Th 2对慢病毒复制的控制 对包膜抗原的反应。