IMPACT OF HUMAN MAB AGAINST HCV E2 SURFACE GLYCOPROTIEN ON HCV INFECTION

抗 HCV E2 表面糖蛋白的人单克隆抗体对 HCV 感染的影响

• 批准号: 8172705
• 负责人: Robert E LANFORD
• 金额: $ 4.16万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172705
• 关键词: Animals; Antibodies; Biological Assay; Cell Culture Techniques; Clinical; Computer Retrieval of Information on Scientific Projects Database; Dose; Epitopes; Funding; Genome; Genotype; Glycoproteins; Grant; Hepatitis C; Hepatitis C virus; Human; In Vitro; Infection; Institution; Laboratories; Monoclonal Antibodies; Pan Genus; Research; Research Personnel; Resources; Safety; Source; Surface; United States; United States National Institutes of Health; Viral Load result; base; human monoclonal antibodies; liver transplantation; prevent; therapy development; viral RNA

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. Hepatitis C infection is the leading cause of liver transplantation in the United States and there is an urgent need to develop therapy aimed to reduce rates of re-infection of transplanted livers. The sponsor of this study has developed a fully human monoclonal antibody directed at a linear epitope of the HCV E2 glycoprotein and has shown that this monoclonal antibody effectively neutralizes pseudovirus from HCV genotypes 1a, 1b, 2b, 3a, and 4a, and replication competent HCV in a cell culture assay using HCVcc strain JFH1/J6. Based on these in vitro results, a study was conducted to demonstrate the ability of the monoclonal to prevent HCV infection in uninfected chimpanzees. Three chimpanzees were studied and received either 0mg/kg, 50mg/kg, or 250mg/kg of antibody intravenously approximately 30 minutes prior to challenge with 32 Chimpanzee Infectious Doses (CID) of HCV strain H77. The animals were followed for 20 weeks with weekly PCR based viral load analysis as well as clinical and laboratory safety assessments. The lower limit of quantification of viral RNA was 500 Genomes/mL (Ge/mL).

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。 丙型肝炎感染是美国肝移植的主要原因，迫切需要开发旨在降低移植肝再次感染率的治疗方法。这项研究的发起人开发了一种针对丙型肝炎病毒E2糖蛋白线性表位的全人单抗，并在使用HCVcc株JFH1/J6进行的细胞培养试验中表明，该单抗有效地中和了来自1a、1b、2b、3a和4a型丙型肝炎病毒以及复制能力强的丙型肝炎病毒。基于这些体外结果，进行了一项研究，以证明该单抗能够预防未感染的黑猩猩感染丙型肝炎病毒。对三只黑猩猩进行了研究，在攻击前大约30分钟静脉注射了0 mg/kg、50 mg/kg或250 mg/kg的抗体，用32种黑猩猩感染剂量(CID)的丙型肝炎病毒H77株进行攻击。对这些动物进行了为期20周的跟踪，每周进行一次基于聚合酶链式反应的病毒载量分析以及临床和实验室安全评估。病毒RNA定量下限为500个基因组/毫升(GE/毫升)。