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

• 批准号: 10435356
• 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
• 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/10435356
• 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 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; 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

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.

项目总结