Understanding human antibody responses to chronic viral hepatitis C

了解人类抗体对慢性丙型病毒性肝炎的反应

基本信息

批准号：
10551237
负责人：
Mansun Law
金额：
$ 62.18万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-01-17 至 2026-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10551237
关键词：
2019-nCoV Achievement Affect Antibodies Antibody Response Antigens Antiviral Agents Awareness B-Cell Activation B-Lymphocytes Caring Cell Lineage Cells Chronic Chronic Hepatitis B Chronic Hepatitis C Complement 3d Receptors Data Set Diagnosis Endowment Epitopes Face Generations Genes Genetic Genetic Transcription Glycoproteins Goals HIV Hepatitis Hepatitis B Hepatitis C Hepatitis C Acquisition Hepatitis C virus Human Immune Immune response Immune system Immunogenetics Immunologic Memory Individual Infection Inflammation Information Protection Learning Liver Liver Cirrhosis Longitudinal Studies Lymphocyte Malignant neoplasm of liver Mediating Memory Memory B-Lymphocyte Modeling Molecular Patients Persons Phenotype Population Production Property Public Health Recovery Reporting Risk Sampling Shapes Surface T-Lymphocyte Time Vaccination Vaccines Viral Viral Antibodies Viral hepatitis Virus Virus Diseases adaptive immunity chronic infection experience functional disability genetic signature high risk population immune function influenza virus vaccine influenzavirus liver infection neutralizing antibody prevent receptor response transmission process vaccine development virus envelope

项目摘要

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.

项目概要丙型肝炎病毒 (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。美国过去的新增感染病例有所增加十年来，据估计只有 20% 的丙型肝炎患者了解自己的情况感染，其中只有 15% 得到治疗。虽然直接作用非常有效抗病毒药物 (DAA) 可以治愈 95% 以上的慢性 HCV 患者，但有报道称，有再感染的情况自发或成功清除先前感染的个人治疗。这些观察结果强调，HCV 的免疫记忆是通过感染不能有效防止再感染。指导疫苗的开发和公众保护高危人群的健康策略，了解免疫非常重要 DAA 治愈患者对 HCV 的记忆，特别是交叉中和抗体反应。在这个我们将研究人类记忆 B 细胞反应如何因慢性感染而改变以及接受 DAA 治疗的慢性 HCV 患者的康复情况。我们将调查原因 HCV免疫淋巴细胞在成功后不能保持针对HCV的有效记忆 DAA治疗。我们还将追踪记忆 B 细胞编码的功能和恢复针对患者体内保守病毒中和表位的抗体。这些细胞将是对于预防 HCV 再感染和疫苗接种至关重要。这项研究不仅将提供了了解慢性病影响的人类免疫反应的绝佳机会病毒感染，但也会产生预防 HCV 感染的重要信息。