Understanding human antibody responses to chronic viral hepatitis C

项目总结 丙型肝炎病毒(丙型肝炎病毒)感染约1%的世界人口，使感染者容易感染 增加了患肝硬变和肝癌的风险。美国的新感染病例过去曾有所上升 十年来，估计只有20%的丙型肝炎患者意识到他们的 感染，其中只有15%的人得到了治疗。虽然非常有效的导演 抗病毒药物(DAA)可以治愈95%以上的慢性丙型肝炎患者，有报道称再感染 自发或在成功清除先前感染后清除了先前感染的个人 治疗。这些观察强调了对丙型肝炎病毒的免疫记忆是通过 感染并不能有效地防止再次感染。以指导疫苗和公众的发展 为了保护高危人群的健康战略，了解免疫将是重要的 DAA治愈患者对丙型肝炎病毒的记忆，特别是交叉中和抗体反应。在这 我们将研究慢性感染是如何改变人类记忆B细胞反应的 在接受DAA治疗的慢性丙型肝炎患者中其恢复情况。我们将调查原因 丙型肝炎病毒免疫淋巴细胞在感染丙型肝炎病毒后不能保持有效记忆 DAA治疗。我们还将跟踪记忆B细胞编码的功能和恢复情况 针对患者中保守病毒中和表位的抗体。这些细胞将是 在再感染和疫苗接种中对预防丙型肝炎至关重要。这项研究不仅将 提供了一个极好的机会来了解慢性疾病对人类免疫反应的影响 病毒感染，但也将产生关键的信息，以防止丙型肝炎病毒感染。

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.