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.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在从急性自限性丙型肝炎自然恢复的患者中，通常可以观察到强烈的丙型肝炎病毒特异性T细胞反应。相比之下，T细胞反应较弱，而且集中在持续感染的患者中。有研究认为，在慢性感染者中，增强和/或从头诱导丙型肝炎病毒特异性细胞免疫反应将导致丙型肝炎病毒的清除和恢复。这一假设只能在黑猩猩身上验证，黑猩猩是唯一容易感染丙型肝炎病毒的动物。 我们建议用表达丙型肝炎病毒NS3、NS4和NS5B的重组载体免疫2只丙型肝炎病毒携带者黑猩猩，以诱导丙型肝炎病毒特异性T细胞应答，并评估这些丙型肝炎病毒特异性T细胞是否可以通过减少或消除病毒血症和/或通过控制丙型肝炎病毒抗原的表达来影响丙型肝炎病毒携带者状态。该疫苗有两种成分，一种是重组丙型肝炎病毒痘病毒(MVA-HCV)，另一种是重组丙型肝炎病毒腺病毒(Ad-丙型肝炎病毒)，将在一次强化免疫方案中应用。该疫苗表达3种丙型肝炎病毒抗原，即丙型肝炎病毒NS3、NS4和NS5B。腺病毒和MVA都是已知的强大的T细胞免疫诱导剂。一只携带丙型肝炎病毒的黑猩猩将被模拟接种不表达丙型肝炎病毒抗原的载体。