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.

计划概要 该 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反应。尽管抗病毒药物非常有效 抗丙肝病毒药物现已上市，新感染病例的持续增加凸显了现实世界的现实 在没有疫苗的情况下对抗这种人类感染的挑战。本 P01 提案“广泛有效的肝炎 C 疫苗”建立在这样的假设之上：有效对抗多种循环 HCV 毒株的 HCV 疫苗可以 通过合理设计疫苗来开发，以增强抗原的免疫原性和呈递 保守的中和表位，并靶向明确的多供体类广泛中和抗体 (bnAb) 对 HCV 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疫苗接种产生的功能特征。这个P01程序包括2 研究项目，由一个管理核心和两个科学核心支持。该计划的总体目标是：（1） 确定对于合理疫苗设计很重要的 HCV 包膜糖蛋白结构； (2) 至 合理设计 HCV 疫苗抗原，以引发有效的广泛中和抗体 对抗多种流行病毒株； (3) 测定HCV疫苗引起的抗体反应 临床前动物模型中的抗原。该研究计划的成功将带来基础科学 知识和强大的 HCV 候选疫苗，用于未来的试点生产和临床测试。