DEVELOPMENT OF HEPATITIS C VIRUS-LIKE PARTICLES AS CANDIDATE HCV VACCINE

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来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。目前，还没有预防HCV感染的疫苗可用，并且该流行病在世界范围内继续有增无减。本研究的目的是开发一种由HCV样颗粒组成的候选HCV疫苗，并在黑猩猩模型中评价疫苗的免疫原性。HCV亚型1b和1a正在四只黑猩猩中滴定，以提供疫苗攻击剂量的标准化接种物。在接种1b亚型的三只动物中，一只抵抗了感染，其余两只出现了慢性感染。正在评估所有三种动物的T细胞应答，以了解感染结果的差异，并描述T细胞在保护性免疫中对HCV感染的作用。其余的动物已接种1a亚型，正在监测感染的证据。两个慢性感染的动物被用来确定是否人单克隆抗HCV抗体池能够清除慢性感染。用5 mg/kg剂量的抗体制剂处理动物，并监测其病毒学和免疫学状态。另外4只未感染过HCV的黑猩猩用佐剂和免疫刺激复合物配制的HCV-VLP疫苗免疫。用感染性HCV攻毒接种疫苗的动物，以确定疫苗预防感染的效力。

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. At the present time, no vaccines to prevent infection with HCV are available and the epidemic continues unabated worldwide. The objectives of this study are to develop a candidate HCV vaccine consisting of HCV-like particles and to evaluate the immunogenicity of the vaccine in the chimpanzee model. HCV subtypes 1b and 1a are being titrate in four chimpanzees to provide a standardized inoculum for vaccine challenge dose. Of the three animals inoculated with subtype 1b, one has resisted infection, and the remaining two have developed chronic infections. T cell responses in all three animals are being evaluated to understand the difference in the outcome of the infection and to delineate the role of T cells in protective immunity against HCV infection. The remaining animal has been inoculated with subtype 1a and is being monitored for evidence of infection. Two chronically infected animals are being utilized to determine whether a pool of human monoclonal anti-HCV antibodies is capable of clearing chronic infection. The animals were treated with 5 mg/kg dose of the antibody preparation and their virological and immunological status are being monitored. An additional four HCV na¿ve chimpanzees were immunized with HCV-VLP vaccine formulated with adjuvants and immunostimulatory complexes. The vaccinated animals have been challenged with infectious HCV to determine the efficacy of the vaccine preventing infection.