IMMUNOGENETHERAPY OF CHRONIC HCV CARRIER CHIMPANZEES

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。强有力的HCV特异性T细胞反应通常在急性自限性丙型肝炎自发恢复的患者中观察到。相比之下，T细胞反应较弱，并且仅集中在持续感染的患者中。已经提出在慢性感染个体中增强和/或从头诱导HCV特异性细胞免疫应答将诱导HCV清除和恢复。这一假设只能在黑猩猩身上得到验证，黑猩猩是唯一易受HCV感染的动物。 我们建议用表达HCV NS 3、NS 4和NS 5 B的重组载体接种2只HCV携带者黑猩猩，以诱导HCV特异性T细胞应答，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/或通过控制HCV抗原表达来影响HCV携带者状态。该疫苗有2种组分，重组HCV痘病毒（MVA-HCV）和重组HCV腺病毒（Ad-HCV），并将以初免-加强方案应用。该疫苗表达3种HCV抗原，即HCV NS 3、NS 4和NS 5 B。已知腺病毒和MVA都是T细胞免疫的强诱导剂。将用不表达HCV抗原的载体模拟接种一只HCV携带黑猩猩。

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.