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 科学核心旨在成功招募和监测HCV抗体阴性的注射者 HCV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HCV RNA和血清转换与系列ALT和HCV RNA检测。核心B的基础架构是 这对于完成HCV疫苗在有感染风险的人群中的首次试验是必要的， 在未来可能的HCV疫苗试验中。血浆、血清和外周血单核细胞将被 从感染前、感染期间和感染结果（清除或 病毒持续存在以及再感染期间。样本存储在存储库中，供项目1-4使用， 以及其他HCV研究者。核心B还将提供标准化血清学检测， 人或接种动物血浆或血清中的HCV抗体。定量分析 疫苗诱导的血浆或血清抗体应答的测定对于确定最有前途的疫苗至关重要。 候选人通过将一组标准化的测定应用于接种疫苗后的样品和来自 成功清除多种HCV感染，我们将能够进行定量和定性比较 在小鼠或非人灵长类动物（项目3和5）和人类中， 体内抗HCV的保护性应答（项目2）。这将有助于识别疫苗最 在进行人体试验时可能会起到保护作用。