Humoral Immune Response to Acute HCV Infection

对急性 HCV 感染的体液免疫反应

• 批准号: 7919768
• 负责人: STUART C RAY
• 金额: $ 21.58万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-15 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7919768
• 关键词: Acute; Acute Hepatitis C; Affect; Affinity; Antibody Formation; Autologous; B-Lymphocytes; Biological Assay; CD4 Positive T Lymphocytes; CD8B1 gene; Cells; Clinical; Complementarity Determining Regions; Epitopes; Evolution; Glycoproteins; Hepatitis C; Hepatitis C virus; Human; Immune response; Individual; Infection; Infection prevention; Injecting drug user; Investigation; Knowledge; Longitudinal Studies; Molecular; Mutate; Persons; Phase; Phylogenetic Analysis; Play; Predictive Value; Reaction; Risk; Role; Specimen; Structure of germinal center of lymph node; T-Lymphocyte; Testing; Variant; Viral; Viral Proteins; Viremia; Virus; Work; anti-hepatitis C; base; cohort; fitness; in vitro Assay; in vivo; neutralizing antibody; novel; positional cloning; prospective; response

The primary objective of Project 2 is to expand on our studies of humoral immune response to acute hepatitis C virus (HCV) infection by examining the clinical and molecular correlates of potent neutralizing antibody responses. We have recently demonstrated that anti-HCV neutralizing antibodies drive the evolution of HCV proteins El and E2 during acute infection, indicating that neutralizing antibodies detected in an in vitro assay are capable of reducing viral fitness in vivo. In addition, available evidence from acute Infections indicates that high-titer neutralizing antibody responses are present in persons who go on to clear viremia, and not in those who progress to chronicity. We h3T30thesize that neutralizing antibodies are a predictive marker of clearance of acute HCV infection, and that evasion of these responses is a constrained mechanism for viral persistence. Thus, we propose the following aims to elucidate the clinical utility and basic mechanisms of HCV neutralization: (I) To define the positive predictive value of a potent anti-HCV neutralizing antibody response as a predictor of clearance during acute infection, and (II) To investigate the mechanisms by which HCV evades neutralizing antibody responses during acute infection. Results of studies of cellular immune responses from Project 1 will be integrated to expand knowledge of the interplay between humoral and cellular immune responses to HCV in humans. We have already demonstrated that we can obtain the critical specimens required for this investigation and will be able to conduct unique longitudinal studies of adaptive immune responses in persons transitioning from acute to established infection.

项目2的主要目的是扩展我们对急性肝炎的体液免疫反应的研究 通过检查有效中和抗体的临床和分子相关性，病毒（HCV）感染 回答。我们最近证明，抗HCV中和抗体驱动HCV的演变 急性感染期间蛋白质EL和E2，表明在体外测定中检测到的中和抗体 能够降低体内病毒适应性。此外，急性感染的可用证据表明 高滴度中和抗体反应是在继续清除病毒血症的人中，而不是 谁逐渐发展。我们h3t30the，中和抗体是清除的预测标记 急性HCV感染，逃避这些反应是病毒持久性的受到限制机制。因此， 我们提出以下旨在阐明HCV中和的临床实用性和基本机制：（i）至 定义有效的抗HCV中和抗体反应的阳性预测值作为预测因子 急性感染期间的清除率，以及（ii）研究HCV逃避中和的机制 急性感染期间的抗体反应。项目1的细胞免疫反应研究结果将 集成以扩大对体液和细胞免疫反应之间对HCV的相互作用的知识 人类。我们已经证明我们可以获得此调查所需的关键标本 并能够对过渡的人的自适应免疫反应进行独特的纵向研究 从急性到建立感染。