EVALUATION OF NUCLEIC ACID VACCINE AS A PREVENTIVE AND THERAPEUTIC MODALITY

核酸疫苗作为预防和治疗方式的评价

• 批准号: 2571374
• 负责人: J W SHIH
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2571374
• 关键词: MHC class I antigen; Pan; clinical research; genetic strain; hepatitis C; hepatitis C virus; hepatitis vaccine; human subject; influenza vaccines; laboratory mouse; nucleic acid sequence; polymerase chain reaction; synthetic vaccines; virus DNA; virus genetics

This recent initiative was designed to elucidate the potential uses and pitfalls of a newly recognized modality of vaccination and to extend our long-term effort to study the immune response and clinical sequela of hepatitis C virus (HCV) infection. Genetic immunization was first demonstrated in mice by directly injecting plasmids containing influenza core protein-encoding DNA into muscle. This procedure induced both antibody and cytotoxic T lymphocyte (CTL) responses to influenza, and the induced CTL can protect mice from challenge with heterologous influenza strains. One of the advantages of genetic immunization is that the endogenously expressed proteins can be recognized by class I major histocompatibility complex (MHC) molecules and expressed on the cell surface. The MHC-antigen complex on the cell surface can be recognized by CTLs, which in turn are activated and attack infected cells. The possibility of inducing an immune response to HCV core protein using DNA immunization provides an attractive alternative to classic vaccination. Many problematic issues are related to developing a vaccine for HCV. One of the major concerns is HCV's genetic stability. There are two hypervariable regions in the putative HCV envelope proteins. The immune escape mutants observed were believed to have mutated in these regions. Experimentally infected chimpanzees and HCV patients were found to have repeated bouts of infection with either homologous or new strains of HCV. This finding could be one of the reasons that more than 80 percent of the infections become chronic. Directly induced strong cell mediated immunity, especially using protective CTLs, may not only help to prevent initial HCV infection, it may even serve as an immune modulation to overcome the infection.

最近的这一举措旨在阐明 和新认识的疫苗接种方式的陷阱， 延长我们长期研究免疫反应的努力， 丙型肝炎病毒（HCV）感染的临床后遗症。遗传 通过直接注射， 将含有流感核心蛋白编码DNA的质粒导入肌肉。 该过程诱导抗体和细胞毒性T淋巴细胞 (CTL)诱导的CTL对小鼠有保护作用 从挑战与异源流感病毒株。之一 基因免疫的优点是， 表达的蛋白质可以被I类主要的 组织相容性复合体（MHC）分子并在细胞上表达 面细胞表面上的MHC-抗原复合物可以是 被CTL识别，CTL反过来被激活并攻击感染者， 细胞诱导对HCV核心免疫应答的可能性 使用DNA免疫的蛋白质提供了一种有吸引力的替代方案， 经典的疫苗许多有问题的问题与 研发HCV疫苗其中一个主要的问题是丙型肝炎病毒的 遗传稳定性有两个高变区， 推定的HCV包膜蛋白。观察到的免疫逃逸突变体 在这些区域发生了变异实验 感染的黑猩猩和HCV患者被发现重复 感染同源或新的HCV毒株。 这一发现可能是80%以上的人 的感染变成慢性的。直接诱导强细胞 介导的免疫，特别是使用保护性CTL，可能不仅 有助于预防最初的HCV感染，它甚至可以作为一种 免疫调节以克服感染。