Broadly Effective HCV Vaccine

广泛有效的 HCV 疫苗

• 批准号: 10557871
• 负责人: Mansun Law
• 金额: $ 208.35万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10557871
• 关键词: Animal Model; Animals; Antibodies; Antibody Response; Antibody Specificity; Antigen Presentation; Antigens; Antiviral Agents; Autoimmune; B-Lymphocytes; Binding Sites; Biochemical; Biological Assay; CD81 gene; Case Study; Communication; Complex; Computer Models; Cost efficiency; Electron Microscopy; Electrons; Engineering; Epidemic; Epitope Mapping; Epitopes; Face; Future; Generations; Genes; Genetic; Genetic Variation; Genotype; Glycoproteins; Goals; Hepatitis C; Hepatitis C Vaccine; Hepatitis C virus; Human; Human Volunteers; Immune; Immune response; Immune system; Immunization; Immunize; Infection; Knowledge; Laboratories; Liver Cirrhosis; Macaca; Macaca mulatta; Malignant neoplasm of liver; Maps; Microscopic; Modeling; Mutagenesis; Population; Production; Program Research Project Grants; Reagent; Recombinants; Reproducibility; Research; Research Project Grants; Resolution; Resources; Role; Scanning; Site; Standardization; Structure; Vaccinated; Vaccination; Vaccine Antigen; Vaccine Design; Vaccines; Viral; Viral Envelope Proteins; Virus; Visual; animal resource; biophysical properties; immunogenicity; improved; innovation; interdisciplinary approach; mouse model; nanoparticle; neutralizing antibody; nonhuman primate; novel; polyclonal antibody; pre-clinical; preclinical evaluation; programs; rational design; receptor; receptor binding; research clinical testing; self assembly; single molecule; spatial relationship; success; synergism; vaccine candidate; vaccine development; vaccine immunogenicity; viral transmission; virology; virus envelope

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.

节目概要 P01提案的总体目标是开发新型丙型肝炎病毒（HCV）候选疫苗， 可以在免疫中引发有效的广泛中和抗体应答。尽管有高效的抗病毒药物 尽管目前已有抗HCV药物，但新感染病例的持续增加凸显了现实世界中 在没有疫苗的情况下对抗这种人类感染的挑战。P01提案“广泛有效的肝炎 C疫苗”是建立在这样的假设上的，即针对不同的循环HCV毒株有效的HCV疫苗可以 通过疫苗的合理工程化来开发，以增强抗原免疫原性和 保守中和表位，并靶向明确定义的多供体类广泛中和抗体 （bnAb）对HCV的应答。多供体类抗体应答是共享共同遗传和免疫原性的抗体。 在群体水平上，在感染或接种疫苗时产生的功能特征。本P01程序由2个 研究项目，由一个行政核心和2个科学核心支持。该方案的总体目标是：（1） 确定HCV包膜糖蛋白的结构对疫苗的合理设计具有重要意义; 合理设计HCV疫苗抗原，以激发有效的广泛中和抗体， （3）确定HCV疫苗诱导的抗体应答 临床前动物模型中的抗原。这项研究计划的成功将导致基础科学 知识和强有力的HCV疫苗候选者，用于未来的中试生产和临床试验。