Broadly Effective HCV Vaccine

计划摘要 这项P01提案的首要目标是开发新的丙型肝炎病毒(HCV)候选疫苗， 可在免疫过程中引发有效的广谱中和抗体反应。尽管有高效的抗病毒药物 抗丙型肝炎病毒药物现已面世，新感染病例的持续增加突显了现实世界 在没有疫苗的情况下抗击这种人类感染的挑战。本P01建议“广效肝炎” C疫苗“是建立在一个假设的基础上的，即一种对不同流行的丙型肝炎病毒株有效的丙型肝炎病毒疫苗可以 通过合理设计疫苗来提高抗原的免疫原性和呈递 保守的中和表位，并靶向明确定义的多供体类广泛中和抗体 (BNab)对丙型肝炎病毒的反应。多供体类抗体反应是具有共同遗传和 在人群水平上感染或接种疫苗时产生的功能特征。本P01节目单包含2个 研究项目，由1个行政核心和2个科学核心提供支持。该计划的总体目标是：(1) 确定丙型肝炎病毒包膜糖蛋白的结构对合理的疫苗设计很重要；(2) 合理设计丙型肝炎疫苗抗原，激发有效的广谱中和抗体 针对不同的流行病毒株；(3)检测丙型肝炎病毒疫苗诱导的抗体反应 临床前动物模型中的抗原。这项研究计划的成功将带来两个基本的科学 知识和强大的候选丙型肝炎病毒疫苗，用于未来的中试生产和临床测试。

Program Summary The overarching goal of this P01 proposal is to develop novel hepatitis C virus (HCV) vaccine candidates that can elicit potent broadly neutralizing antibody responses in immunization. Despite highly effective antiviral drugs against HCV now being available, the continuous increase in new infections underscores the real-world challenges in combating this human infection without a vaccine. This P01 proposal “Broadly Effective Hepatitis C Vaccine” is built on the hypothesis that an HCV vaccine effective against diverse circulating HCV strains can be developed through rational engineering of vaccines to enhance antigen immunogenicity and presentation of conserved neutralizing epitopes, and to target well-defined multidonor class broadly neutralizing antibody (bnAb) responses to HCV. Multidonor class antibody responses are antibodies sharing common genetic and functional features produced in infection or vaccination at the population level. This P01 program consists of 2 research projects, supported by an admin core and 2 scientific cores. The overall aims of the program are: (1) To determine the structures of HCV envelope glycoproteins important for rational vaccine design; (2) To rationally design HCV vaccine antigens for elicitation of broadly neutralizing antibodies that will be effective against diverse circulating viral strains; (3) To determine the antibody responses elicited by HCV vaccine antigens in preclinical animal models. Success in this research program will result in both basic scientific knowledge and a strong HCV vaccine candidate for future pilot production and clinical testing.