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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 在从急性，自限制的乙型肝炎中自发恢复的患者中，通常观察到剧烈的HCV特异性T细胞反应。相反，T细胞反应较弱且狭窄地集中在持续感染的患者中。 已经提出，长期感染的个体中HCV特异性细胞免疫反应的增强和/或从头诱导将诱导HCV清除和恢复。 该假设只能在黑猩猩中检验，这是唯一容易受到HCV感染的动物。 我们提议用表达HCV NS3，NS4和NS5B的重组载体接种2 HCV载体，以诱导HCV特异性T细胞反应并评估这些HCV特异性T细胞可以通过减少病毒蛋白酶和/或消除HCV蚂蚁的表达来影响HCV特异性T细胞对HCV载体状态的影响。 该疫苗具有2个成分，一个重组HCV痘病毒（MVA-HCV）和一个重组HCV腺病毒（AD-HCV），并将用于促进型方案。 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。 一个HCV载体黑猩猩将通过未表达HCV抗原的向量进行模拟疫苗。