CYTOKINE MODULATION OF LENTIVIRAL DNA VACCINES

描述(改编自申请人的摘要)：本提案涉及 利用嗜巨噬细胞慢病毒的慢病毒接种策略 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囊膜蛋白的DNA。研究计划是基于WELL的 有记录的小鼠研究表明，交叉调节细胞因子 明确Th1和Th2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 子集反应可以在实验上控制在远缘繁殖的基因上 背景由细胞因子引导的启动，一个潜在的重要概念 艾滋病毒疫苗设计。因此，要检验的假设是该表达式 编码山羊白介素12或干扰素-γ的质粒会增强 CAEV env表达载体对Th1细胞的免疫应答 编码山羊白介素4的质粒DNA将增强抗原特异性 Th2反应。预期结果将使CAEV挑战实验能够 评价极化Th1和Th2对慢病毒复制的控制作用 对包膜抗原的反应。

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.