Mechanisms of spontaneous and vaccine mediated hepatitis C virus control to direct rational development of a novel HCV vaccine

自发和疫苗介导的丙型肝炎病毒控制机制指导新型丙型肝炎疫苗的合理开发

• 批准号: 10398149
• 负责人: ANDREA L COX
• 金额: $ 47.33万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10398149
• 关键词: Acute; Acute Hepatitis C; Aliquot; Animals; Antibodies; Antibody Response; Antibody titer measurement; Binding; Biological Assay; Biological Specimen Banks; Blood; Blood Component Removal; Cells; Clinical; Code; Collection; Counseling; Development; Elements; Enrollment; Ensure; Enzyme-Linked Immunosorbent Assay; Experimental Models; Funding; Future; Genotype; Goals; Grant; Harm Reduction; Hepatitis C; Hepatitis C Antibodies; Hepatitis C Incidence; Hepatitis C Vaccine; Hepatitis C virus; Human; Immune response; Immunity; Infection; Infrastructure; Injecting drug user; Location; Lymphocyte; Macaca; Measurement; Measures; Mediating; Mediator of activation protein; Monitor; Monoclonal Antibodies; Mus; Neutralization Tests; Outcome; Participant; Peripheral Blood Mononuclear Cell; Persons; Pharmacotherapy; Phase; Phylogenetic Analysis; Plasma; Population; RNA; Recovery; Recurrence; Research; Research Personnel; Resources; Risk; Sampling; Scientist; Serology test; Serum; Specimen; Standardization; Testing; Time; United States National Institutes of Health; Vaccinated; Vaccination; Vaccines; Viremia; Virus; Visit; acute infection; chronic infection; clinical care; clinically relevant; cohort; design; efficacy trial; env Gene Products; experimental study; high risk; immunogenicity; in vivo; infection risk; injection drug use; nonhuman primate; novel; outreach; prophylactic; prospective; recruit; repository; response; screening; seroconversion; success; treatment program; vaccine candidate; vaccine evaluation; vaccine-induced antibodies

Scientific Core (Core B) Project Summary The Scientific Core is designed to successfully recruit and monitor HCV-antibody-negative people who inject drugs (PWID) for HCV infection and to identify and characterize acute infections and reinfections by testing sera for HCV RNA and seroconversion with serial ALT and HCV RNA testing. The infrastructure of Core B was necessary for completion of the first trial of an HCV vaccine in people at risk of HCV infection and will be useful in potential future trials of HCV vaccines. Plasma, serum, and peripheral blood mononuclear cells will be collected from prior to infection, during infection, and through the time when infection outcome (clearance or persistence of virus as well as during reinfection. Samples are stored in the repository for use in Projects 1-4, as well as for other HCV investigators. Core B will also provide standardized serological testing to quantitate HCV envelope-specific antibodies in plasma or serum of humans or vaccinated animals. Quantitative analyses of vaccine-induced plasma or serum antibody responses are essential to identify the most promising vaccine candidates. By applying a standardized set of assays to samples post-vaccination and from humans who successfully cleared multiple HCV infections, we will be able to make quantitative and qualitative comparisons between vaccine-induced antibody responses in mice or nonhuman primates (Projects 3 and 5) and human responses that are protective against HCV in vivo (Project 2). This will facilitate identification the vaccines most likely to be protective when advanced to human trials.

科学核心(核心B)项目摘要 Science Core旨在成功招募和监控注射丙型肝炎病毒抗体阴性的人 治疗丙型肝炎病毒感染的药物(PWID)，并通过检测来识别和表征急性感染和再感染 血清进行丙型肝炎病毒核糖核酸检测和血清转换及丙氨酸氨基转移酶和丙型肝炎病毒核糖核酸检测。核心B的基础设施是 对于完成丙型肝炎病毒感染风险人群的丙型肝炎疫苗的第一次试验是必要的，并且将是有用的 在未来潜在的丙型肝炎疫苗试验中。血浆、血清和外周血单核细胞将 收集自感染前、感染期间和感染发生时(清除或 病毒的持久性以及在再次感染期间。样本存储在储存库中以在项目1-4中使用， 以及其他丙型肝炎病毒研究人员。核心B还将提供标准化的血清学检测，以量化 人或接种疫苗的动物的血浆或血清中的丙型肝炎病毒包膜特异性抗体。定量分析 疫苗诱导的血浆或血清抗体反应是确定最有希望的疫苗的关键 候选人。通过将一套标准化的化验应用于疫苗接种后的样本和来自 成功清除多个丙型肝炎病毒感染，我们将能够进行定量和定性比较 疫苗在小鼠或非人灵长类动物中诱导的抗体反应(项目3和5)与人类之间的关系 体内对丙型肝炎病毒具有保护性的反应(项目2)。这将最有利于疫苗的鉴定 很可能在进入人体试验时起到保护作用。