Understanding human neutralizing antibodies to hepatitis C virus

了解人类丙型肝炎病毒中和抗体

• 批准号: 8579834
• 负责人: Mansun Law
• 金额: $ 53.79万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-15 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8579834
• 关键词: Adopted; Adverse effects; Animal Model; Antibodies; Antibody Formation; Antiviral Agents; B-Lymphocytes; Caring; Cause of Death; Clinical; Developed Countries; Dose; Drug Formulations; Drug usage; Epitopes; Evaluation; Foundations; Genotype; Goals; HCV screening; HIV; Healthcare; Hepatitis B; Hepatitis B Virus; Hepatitis C; Hepatitis C Antibodies; Hepatitis C virus; Human; Immunoglobulin G; Immunoglobulins; Immunotherapeutic agent; Immunotherapy; In Vitro; Infection; Infection prevention; Interferons; Investigation; Laboratories; Lamivudine; Lead; Length; Life; Liver Failure; Liver diseases; Malignant neoplasm of liver; Memory B-Lymphocyte; Methods; Molecular; Monoclonal Antibodies; Passive Immunotherapy; Patients; Phage Display; Phase II Clinical Trials; Population; Prevention; Prevention strategy; Property; Receptor Gene; Receptors, Antigen, B-Cell; Recurrence; Research; Ribavirin; Site; Staging; Surveys; Symptoms; System; Technology; Time; Transplant Recipients; Transplantation; United States National Institutes of Health; Universities; Viral; Viral Antibodies; Viral hepatitis; Virus; age group; base; chronic liver disease; cost; hepatitis C virus envelope 2 protein; high risk; human monoclonal antibodies; immunosuppressed; improved; in vivo; liver transplantation; mortality; mouse model; neutralizing antibody; novel; passive antibodies; prevent; programs; public health relevance; screening; small molecule

DESCRIPTION (provided by applicant): One of the research goals highlighted in the Action Plan for Liver Disease of the National Institutes of Health is to develop means, including anti-viral antibodies, to prevent recurrence of hepatitis C virus (HCV) after liver transplantation. HCV associated liver failure is the most common indication for liver transplantation but recurren HCV invariably occurs after transplantation and can lead to rapid graft loss. The immunosuppressed liver transplant recipients tolerate the side effects of IFN-¿ and ribavirin poorly and therefore new strategies for prevention and/or treatment of HCV in the transplant setting are urgently required. The long-term objective of this application is to develop an effective and tolerable antibody cocktail to prevent recurrent HCV, and the same treatment may also be useful in preventing infection in the cases of accidental virus exposure of healthcare/laboratory workers, or in high risk populations. The specific aims are (i) to generate human monoclonal antibodies (mAbs) to diverse conserved neutralizing viral epitopes of HCV by phage-display antibody technology; (ii) to generate highly potent HCV neutralizing antibodies by function screen; (iii) to understand the mechanisms of virus neutralization by the antibodies; (iv) to evaluate the efficacy of the mAbs in protecting a recently developed genetically humanized mouse model for HCV study upon challenges by multiple heterologous HCV genotypes. A demonstration of significant protection by the antibody or antibody cocktail would provide the scientific foundation for further investigation of this passive antibody approach in th prevention of recurrent HCV in clinical settings.

描述（由申请人提供）：美国国立卫生研究院肝病行动计划强调的研究目标之一是开发包括抗病毒抗体在内的手段，以防止肝移植后丙型肝炎病毒（HCV）的复发。丙肝病毒