Understanding human antibody responses to chronic viral hepatitis C

项目摘要 丙型肝炎病毒（HCV）感染约1%的世界人口，使感染者易感 增加患肝硬化和肝癌的风险。美国的新感染病例过去有所上升 十年来，据估计，只有20%的丙型肝炎患者知道他们的病情。 感染，只有15%的人得到了治疗。虽然高效的直接作用 抗病毒药物（DAA）可以治愈95%以上的慢性HCV患者， 自发或在成功治疗后清除了先前感染的个体 治疗这些观察结果强调，通过免疫记忆获得的HCV 感染对再感染无效。为了指导疫苗的开发， 为了保护高风险人群的健康战略，了解免疫接种将是重要的。 DAA治愈患者对HCV的记忆，特别是交叉中和抗体应答。在这 我们将研究人类记忆B细胞反应如何被慢性感染改变 以及接受DAA治疗的慢性HCV患者的恢复情况。我们将调查原因 HCV免疫淋巴细胞在成功免疫后不能保持对HCV的有效记忆。 DAA治疗。我们还将跟踪记忆B细胞的功能和恢复， 靶向患者中保守的病毒中和表位的抗体。这些细胞将 对于在再感染和疫苗接种中保护免受HCV至关重要。这项研究不仅将 提供了一个很好的机会，了解人类免疫反应的影响， 病毒感染，但也将产生针对HCV感染的保护的关键信息。

PROJECT SUMMARY Hepatitis C virus (HCV) infect ~1% of the world population, predisposing the infected individuals to increased risk of liver cirrhosis and liver cancer. New infections in the US has risen in the past decade and it is estimated that only 20% of the individuals with hepatitis C are aware of their infection, and only 15% of those have been treated. Although highly effective direct-acting antivirals (DAAs) can cure over 95% chronic HCV patients, reinfections have been reported in individuals who have cleared a previous infection either spontaneously or after a successful treatment. The observations underscore that immune memory to HCV acquired through infection is not effective against reinfection. To guide the development of a vaccine and public health strategy to protect high-risk populations, it will be important to understand immune memory to HCV in DAA-cured patients particularly cross-neutralizing antibody response. In this project we will investigate how human memory B cell response is altered by chronic infection and its recovery in chronic HCV patients undergoing DAA treatment. We will investigate why HCV-immune lymphocytes do not maintain an effective memory against HCV after successful DAA treatment. We will also track the functions and recovery of memory B cells encoding for antibodies targeting conserved virus neutralizing epitopes in the patients. These cells will be crucial for protection against HCV both in reinfection and in vaccination. This study will not only provide an excellent opportunity to learn about human immune response impacted by chronic viral infection but will also generate critical information for the protection against HCV infection.