IMMUNOGENETHERAPY OF CHRONIC HCV CARRIER CHIMPANZEES

慢性 HCV 携带者黑猩猩的免疫基因治疗

• 批准号: 7562457
• 负责人: KRISHNA H MURTHY
• 金额: $ 7.09万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7562457
• 关键词: Acute; Adenoviruses; Animals; Antigens; Carrier State; Chronic; Computer Retrieval of Information on Scientific Projects Database; Funding; Grant; Hepatitis C; Hepatitis C virus; Immune response; Immunity; Individual; Institution; Pan Genus; Pan troglodytes; Patients; Poxviridae; Recombinants; Recovery; Research; Research Personnel; Resources; Source; T-Lymphocyte; Testing; Treatment Protocols; United States National Institutes of Health; Vaccinated; Vaccines; Viremia; doxorubicin/mitomycin/vinblastine protocol; response; vector

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Vigorous HCV-specific T cell responses are typically observed in patients who recover spontaneously from acute, self-limited hepatitis C. In contrast, T cell responses are weak and narrowly focused in persistently infected patients. It has been proposed that enhancement and/or de novo induction of HCV-specific cellular immune responses in chronically infected individuals will induce HCV clearance and recovery. This hypothesis can only be tested in chimpanzees, the only animals susceptible to HCV infection. We propose to vaccinate 2 HCV carrier chimpanzees with recombinant vectors expressing HCV NS3, NS4 and NS5B to induce HCV-specific T cell responses and to evaluate whether these HCV-specific T cells can impact on HCV carrier state, by reducing or eliminating viremia and/or by controlling HCV antigen expression. The vaccine has 2 components, a recombinant HCV pox-virus (MVA-HCV) and a recombinant HCV adenovirus (Ad-HCV), and will be applied in a prime-boost regimen. The vaccine expresses 3 HCV antigens, namely HCV NS3, NS4 and NS5B. Both adenoviruses and MVA are known to be strong inducers of T-cell immunity. One HCV carrier chimpanzee will be mock vaccinated with vectors that do not express the HCV antigens.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 通常在急性自限性丙型肝炎自发恢复的患者中观察到强烈的 HCV 特异性 T 细胞反应。相反，在持续感染的患者中，T 细胞反应较弱且集中。 已经提出，在慢性感染个体中增强和/或从头诱导HCV特异性细胞免疫反应将诱导HCV清除和恢复。 这一假设只能在黑猩猩身上进行检验，黑猩猩是唯一易受丙型肝炎病毒感染的动物。 我们建议用表达 HCV NS3、NS4 和 NS5B 的重组载体对 2 只 HCV 携带者黑猩猩进行疫苗接种，以诱导 HCV 特异性 T 细胞反应，并评估这些 HCV 特异性 T 细胞是否可以通过减少或消除病毒血症和/或控制 HCV 抗原表达来影响 HCV 携带者状态。 该疫苗由重组丙型肝炎病毒痘病毒（MVA-HCV）和重组丙型肝炎病毒腺病毒（Ad-HCV）两种成分组成，将用于初免-加强方案。 该疫苗表达3种HCV抗原，即HCV NS3、NS4和NS5B。 已知腺病毒和 MVA 都是 T 细胞免疫的强诱导剂。 一只 HCV 携带者黑猩猩将使用不表达 HCV 抗原的载体进行模拟疫苗接种。