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

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。目前，没有预防感染丙型肝炎病毒的疫苗可用，这种流行病在全球范围内继续有增无减。本研究的目的是开发一种由类丙型肝炎病毒颗粒组成的候选丙型肝炎病毒疫苗，并在黑猩猩模型中评价该疫苗的免疫原性。丙型肝炎病毒1b和1a亚型正在四只黑猩猩身上进行滴定，以提供疫苗挑战剂量的标准化接种。在接种了亚型1b的三只动物中，一只已经抵抗感染，其余两只发展为慢性感染。正在对所有三种动物的T细胞反应进行评估，以了解感染结果的差异，并描述T细胞在抵御丙型肝炎病毒感染的保护性免疫中的作用。其余的动物已经接种了1a亚型疫苗，正在监测是否有感染的证据。两只慢性感染的动物正在被用来确定一组人类抗丙型肝炎病毒单抗是否能够清除慢性感染。这些动物被注射了5毫克/公斤剂量的抗体制剂，并正在监测它们的病毒学和免疫学状态。用含有佐剂和免疫刺激复合体的丙型肝炎病毒VLP疫苗免疫另外4只丙型肝炎病毒纯种黑猩猩。接种疫苗的动物已经接受了传染性丙型肝炎病毒的攻击，以确定疫苗预防感染的效果。

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.