CYTOKINE MODULATION OF LENTIVIRAL DNA VACCINES

慢病毒 DNA 疫苗的细胞因子调节

• 批准号: 2878029
• 负责人: WILLIAM P CHEEVERS
• 金额: $ 17.4万
• 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 2000-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2878029
• 关键词: Lentivirus; Retroviridae disease; goats; helper T lymphocyte; interferon gamma; interleukin 12; interleukin 4; microorganism immunology; nonhuman therapy evaluation; plasmids; vaccine development; vector vaccine; virus DNA; virus antigen; virus envelope; virus genetics; virus protein; virus replication

The proposal addressees 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 crossregulatory 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 Th1 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 Th1 and Th2 responses to envelope antigens.

该提案涉及慢病毒疫苗接种策略， 山羊关节炎-脑炎病毒 （CAEV），特别是Th淋巴细胞引发的细胞因子调节 用编码CAEV包膜的质粒DNA免疫启动 proteins.这项研究计划是基于有据可查的鼠类研究 表明交叉调节细胞因子指定了 Th 1和Th 2淋巴细胞亚群在抗原呈递时的变化。 这一原理表明，抗原特异性Th亚群应答可 在远交的遗传背景上进行实验控制， 细胞因子导向的引发，HIV中潜在的重要概念 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 用CAEV env表达增强对免疫的Th 1应答 质粒，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应答。预期结果将 允许进行CAEV攻毒实验以评价慢病毒的控制 通过对包膜抗原的极化Th 1和Th 2应答进行复制。