Human/Pig Model of Hepatitis C Virus for New Vaccines

新疫苗的丙型肝炎病毒人/猪模型

• 批准号: 6735244
• 负责人: WILLIAM Edward BESCHORNER
• 金额: $ 31.6万
• 依托单位: XIMEREX, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6735244
• 关键词: clinical research; disease /disorder model; genetically modified animals; hepatitis C; hepatitis C virus; hepatitis vaccine; host organism interaction; human subject; immune response; liver cells; liver cirrhosis; liver disorder; longitudinal animal study; model design /development; pathologic process; questionnaires; swine; virulence; virus infection mechanism; virus replication

DESCRIPTION (provided by applicant): Hepatitis C virus (HCV) has emerged as a major public health problem. World wide, as many as 200 million people are infected. In the United States, an estimated 3.9 million are infected, with 2.7 million Americans chronically infected. The immune response of the patient determines if the patient is cured of the virus, develops a lifelong infection, or develops severe liver disease. Progress in the treatment and prevention of HCV is severely hampered by the lack of a suitable animal model. Chimpanzees are the only animals other than humans that are infected with HCV. The pathogenesis differs from human hepatitis, however. Furthermore, the ethics and availability of chimpanzees limits the studies that can be done. A promising model was recently developed by engrafting human hepatocytes in immune deficient mice. This model, however, cannot assess the immune response to the virus or vaccines. We have developed technology for engrafting human liver cells in immune competent pigs. The innovations include transplanting cells into fetal pigs in utero and the development of unique transgenic pigs that enhance the growth of human liver cells. This study will inoculate HCV into hybrid swine with human liver cells and evaluate the virus proliferation, monitor the persistence of the virus and liver disease, and characterize the immune response. A large animal immune compentent model of HCV will lead to a better understanding of the pathogenesis of hepatitis C virus and to more effective vaccines and immune therapy.

描述（由申请人提供）：丙型肝炎病毒（HCV）已成为主要的公共卫生问题。全世界，多达2亿人被感染。在美国，估计有390万次感染，有270万美国人长期感染。患者的免疫反应确定患者是否治愈了病毒，发展终生感染或发展为严重的肝病。缺乏合适的动物模型，严重阻碍了HCV治疗和预防的进展。 黑猩猩是被HCV感染的人以外的唯一动物。但是，发病机理与人类肝炎不同。此外，黑猩猩的伦理和可用性限制了可以完成的研究。最近，通过在免疫缺陷小鼠中雕刻人肝细胞开发了一个有希望的模型。但是，该模型无法评估对病毒或疫苗的免疫反应。 我们已经开发了用于在免疫能力猪中植入人肝细胞的技术。这些创新包括将细胞移植到子宫内的胎儿猪中，并发展独特的转基因猪，从而增强了人类肝细胞的生长。 这项研究将将HCV与人肝细胞接种到杂化猪中，并评估病毒增殖，监测病毒和肝病的持久性，并表征免疫反应。 大型动物免疫统计模型的HCV模型将使人们更好地了解丙型肝炎病毒的发病机理以及更有效的疫苗和免疫治疗。