权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

First-in-human study of a potent anti-HBsAg neutralizing antibody

强效抗 HBsAg 中和抗体的首次人体研究

基本信息

批准号：
10550458
负责人：
Marina Caskey
金额：
$ 86.47万
依托单位：
ROCKEFELLER UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-03-20 至 2027-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10550458
关键词：
Acceleration Aftercare Amino Acids Animal Model Animals Antibodies Antigen-Antibody Complex Antigens Antiviral Agents Antiviral Therapy B-Lymphocytes Binding CD4 Positive T Lymphocytes CD8-Positive T-Lymphocytes CD8B1 gene Cell-Mediated Cytolysis Cells Cellular Immunity Chronic Chronic Hepatitis B Circular DNA Clinic Clinical Clinical Research DNA Integration Development Disease remission Dose Drug Kinetics Epitopes Event Experimental Models Exposure to Fc domain Fostering Genome HIV-1 Half-Life Hepatitis B Antibodies Hepatitis B Surface Antigens Hepatitis B Virus Hepatitis B e Antigens Human Biology Humoral Immunities IgG1 Immune Immune response Immunity Immunologics Immunotherapy Impairment In Vitro Individual Infection Infection Control Inflammation Innate Immune Response Liver Liver Cirrhosis Measures Mediating Membrane Modeling Modification Monoclonal Antibodies Passive Transfer of Immunity Persons Phagocytosis Pharmacologic Substance Primary carcinoma of the liver cells Rattus Recombinants Recovery Role Safety Serotyping Serum T-Lymphocyte Testing Therapeutic Tissues Transgenic Mice Vaccination Vaccinee Variant Viral Viral Antigens Viral Physiology Viremia Virus Virus Diseases Virus Replication acute infection adaptive immune response analog cancer cell cancer therapy chronic infection cross reactivity exhaustion experience experimental study extracellular first-in-human global health human monoclonal antibodies human study immunoregulation in vivo inflammatory marker manufacture nano neutralizing antibody nonhuman primate novel therapeutic intervention peripheral blood recruit response restoration seroconversion viral RNA

项目摘要

Project Summary Hepatitis B virus (HBV) remains a major global health problem and chronic HBV (CHB) is a major cause of liver cirrhosis and hepatocellular carcinoma. While antiviral therapies achieve long-term viral suppression, they can rarely clear the infection or achieve a state of functional cure where long-term viral suppression is maintained in the absence of treatment. Along with persistence of viral antigens, impaired HBV-specific immunity contributes to the chronicity of infection. Chronic exposure to high levels of HBsAg may render HBV- specific immune cells overly activated and functionally tolerized Thus, decreasing serum HBsAg could be a valuable therapeutic strategy, due to its potential to alleviate functional exhaustion and confer immune control. Passive transfer of antibodies is a potential strategy in CHB for their dual functionality. Antibodies differ from direct-acting antivirals in that they can recruit immune effector functions through their Fc domains to accelerate clearance of viruses and infected cells. In addition, immune complexes are potent immunogens that can foster development of host immune responses. HepB monoclonal antibody (mAb)19 is a human monoclonal antibody to the a-determinant of the extracellular loop of HBsAg and binds the major HBV serotypes. HepB mAb19 showed exceptional in vitro neutralization activity with IC50 in the nanogram range and in vivo antiviral activity in an animal model of infection. The object of this proposal is to conduct a first-in-human dose-escalation study of a long-acting variant of HepB mAb19 in individuals with CHB on antiviral nucleos(t)ide analogue (NRTI) therapy. The hypothesis to be tested is that the administration of HepB mAb19-LS during suppressive NRTI therapy will be safe and well tolerated, will lead to decreased levels of circulating HBsAg, and enhance host innate and adaptive immune responses to HBV.

项目总结