Humoral Immune Response to Acute HCV Infection

项目2的主要目的是扩大我们对急性丙型肝炎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， 应答我们最近证明，抗HCV中和抗体驱动HCV的进化 蛋白E1和E2，表明在体外测定中检测到的中和抗体 能够降低病毒在体内的适应性。此外，现有的急性感染证据表明， 高滴度中和抗体反应存在于继续清除病毒血症的人中，而不存在于那些 会发展成慢性病我们认为，中和抗体是一个预测性标志物的清除， 急性HCV感染，并且逃避这些应答是病毒持续存在的一种受限制的机制。因此，在本发明中， 我们提出以下目的来阐明HCV中和的临床效用和基本机制：（I）为了 将有效抗HCV中和抗体应答的阳性预测值定义为 清除急性感染期间，和（II）探讨HCV逃避中和的机制 急性感染时的抗体反应。项目1的细胞免疫反应研究结果将 整合以扩大对HCV的体液和细胞免疫应答之间相互作用的知识， 人类我们已经证明，我们可以获得这项研究所需的关键标本 并将能够进行独特的纵向研究的适应性免疫反应的人过渡 从急性感染到确诊感染

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.