CYTOKINE MODULATION OF LENTIVIRAL DNA VACCINES

该提案涉及慢病毒疫苗接种战略，使用 巨噬细胞嗜性慢病毒山羊关节炎-脑炎病毒 (CAEV)，Th淋巴细胞预激的特异性细胞因子调节 用编码CAEV囊膜的质粒DNA免疫启动 蛋白质。该研究计划是基于有充分记录的小鼠研究。 证明了交叉调节细胞因子指定了分化 抗原呈递时Th1和Th2淋巴细胞亚群的变化。 这一原理表明，抗原特异性Th亚群反应可以 在远缘繁育的遗传背景下被实验控制 细胞因子定向启动--HIV的一个潜在的重要概念 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 表达CAEV env增强Th1细胞免疫应答 而编码山羊白介素4的质粒DNA将 增强抗原特异性Th2反应。预期结果将 允许CAEV挑战实验评估慢病毒的控制 通过极化Th1和Th2对包膜抗原的反应进行复制。

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.