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

HCV抗体反应和疫苗抗原研究合作中心

• 批准号: 9248879
• 负责人: Mansun Law
• 金额: $ 91.87万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9248879
• 关键词: Animal Model; Antibodies; Antibody Response; Antigen Targeting; Antigens; B cell repertoire; B-Cell Development; B-Lymphocytes; Biological; Biological Assay; Caring; Cavia; Cell Lineage; Clinical; Communicable Diseases; Communication; Data Set; Development; Environment; Epidemic; Epitopes; Foundations; Future; Genetic; Genetic Variation; Genotype; Glycoproteins; Goals; Health system; Hepatitis C; Hepatitis C Antibodies; Hepatitis C Transmission; Hepatitis C Vaccination; Hepatitis C Vaccine; Human; Immune; Immune system; Immunization; Immunize; In Vitro; Infection; Knowledge; Label; Laws; Liver; Liver Cirrhosis; Malignant neoplasm of liver; Maps; Measures; Molecular Probes; Mus; National Institute of Allergy and Infectious Disease; Pathway interactions; Patients; Phase I Clinical Trials; Play; Population; Pre-Clinical Model; Productivity; Protein Engineering; Public Health; Reagent; Research; Research Activity; Research Institute; Research Project Grants; Sampling; Ships; Site; Solid; Specificity; Structure; T cell response; T-Lymphocyte; Vaccinated; Vaccination; Vaccine Antigen; Vaccine Design; Vaccines; Viral; Virus; base; design; efficacy study; high risk population; neutralizing antibody; next generation sequencing; nonhuman primate; novel; particle; pre-clinical; prevent; programs; public health relevance; response; skills; tool; tool development; traditional care; vaccine candidate; viral transmission; virus genetics

 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.

 描述（由适用提供）：HCV感染几乎占世界人口的3％，通常被称为无声流行。它是肝硬化和癌症的主要原因，直到肝功能障碍迹象发生迹象之前，许多感染的人才不知道感染。尽管最近在病毒治疗中取得了重大进展，但没有疫苗可以阻止病毒传播。该计划项目的中心假设是，尽管病毒遗传多样性，但疫苗引起的有效广泛中和抗体反应将有效防止高风险种群的HCV传播。项目1将研究已在上一期临床试验中通过E1E2抗原和已感染HCV接种的人类的抗体反应。同时，将研究用E1E2抗原接种的临床前动物模型中的抗体和B细胞反应，并将其与人类研究进行比较。该研究项目将产生有关抗体，B细胞谱系和HCV免疫表位的全面数据，以指导理性疫苗设计工作。该项目将由Mansun Law博士指导。项目2将利用最近的结构 有关HCV的信息广泛中和表位和计算蛋白设计的进步，以开发以表位为中心的免疫原子及其颗粒形式作为疫苗抗原，以引起对配置免疫表皮的中和抗体反应。该项目将由Jiang Zhu博士领导。这两个项目将利用法律实验室中开发的抗体和病毒试剂，该试剂将由管理员核心管理。 PI还将以其完整的技能相互协助。 Law博士将提供有关HCV，中和抗体和免疫抑制动物模型的专业知识。朱博士将在B细胞库和免疫原设计的下一代测序方面提供专业知识。管理员核心将通过照顾所有行政职责来支持他们的沟通和生产力 作为协调的研究活动，包括实验室和协作站点之间的样本组织，运输和存储。在内部和外部专家的宝贵建议的指导下，团队的联合专家和努力为加速发现了承诺的HCV疫苗候选者提供了坚实的基础。