Cooperative Center for the study of HCV antibody responses and vaccine antigens

 描述（由申请人提供）：HCV感染了近3%的世界人口，通常被称为沉默的流行病。它是肝硬化和癌症的主要原因，许多感染者直到出现肝功能障碍的迹象才意识到感染。虽然最近在病毒治疗方面取得了重大进展，但没有疫苗可以阻止病毒传播。本计划项目的中心假设是，尽管存在病毒遗传多样性，但诱导强效广泛中和抗体应答的疫苗将有效预防高危人群中的HCV传播。项目1将研究在先前的I期临床试验中接种E1E2抗原的人和感染HCV的人的抗体应答。同时，将研究接种E1 E2抗原的临床前动物模型中的抗体和B细胞应答，并与人体研究进行比较。这项研究计划将产生一个全面的数据集的抗体，B细胞谱系，和HCV免疫表位，以指导合理的疫苗设计工作。该项目将由Mansun Law博士指导。项目2将利用最近的结构性 关于HCV广泛中和表位的信息和计算机蛋白质设计的进展，以开发表位聚焦的免疫原及其颗粒形式作为疫苗抗原，以引发对保守免疫表位的中和抗体应答。该项目将由朱江博士领导。这两个项目将利用法律实验室开发的抗体和病毒试剂，由管理核心管理。PI还将以其互补的技能在其项目中相互协助。罗博士将提供关于丙型肝炎病毒，病毒中和抗体和免疫动物模型的专业知识。朱博士将在B细胞库的下一代测序和免疫原设计方面提供专业知识。行政核心将促进他们的沟通和生产力的照顾，以及所有行政职务 作为协调研究活动，包括样品组织，运输和实验室和合作地点之间的存储。在内部和外部专家的宝贵建议指导下，该团队的专业知识和努力为加速发现有前途的HCV候选疫苗提供了坚实的基础。

 DESCRIPTION (provided by applicant): HCV infects nearly 3% of the world population and is often referred as a silent epidemic. It is a leading cause of liver cirrhosis and cancer, and many infected are not aware of the infection until signs of liver malfunction develop. Although significant progress has been made recently in virus treatment, there is no vaccine to stop virus transmission. The central hypothesis for this Program Project is that a vaccine inducing potent broadly neutralizing antibody responses will be effective in preventing HCV transmission in high risk population despite of the virus genetic diversity. Project 1 will study the antibody response in humans who have been vaccinated by the E1E2 antigen in a previous Phase 1 Clinical Trial, and in humans who have been infected by HCV. In parallel, antibody and B cell responses in preclinical animal models vaccinated with E1E2 antigens will be studied and compared to the human studies. This research project will produce a comprehensive set of data on the antibodies, B cell lineages, and HCV immune epitopes to guide rational vaccine design effort. This project will be directed by Dr. Mansun Law. Project 2 will capitalize on the recent structural information on HCV broadly neutralizing epitopes and advances in computational protein design to develop epitope-focused immunogens and their particle forms as vaccine antigens to elicit neutralizing antibody responses to the conserved immune epitopes. This project will be led by Dr. Jiang Zhu. The two projects will utilize antibody and viral reagents developed in the Law lab, which will be managed by an Admin Core. The PIs will also assist each other in their projects with their complementary skills. Dr. Law will provide expertise on HCV, virus neutralizing antibodies, and animal models for immunization. Dr. Zhu will provide expertise in next-generation sequencing of B cell repertoire and immunogen design. The Admin Core will facilitate their communication and productivity by taking care of all administrative duties as well as coordinating research activities including sample organization, shipment and storage between the labs and the collaborative sites. The combined expertise and effort of the team, guided by the valuable advice from internal and external experts, provide a solid foundation to accelerate the discovery of promising HCV vaccine candidates.