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

基本信息

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
项目类别：
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

项目摘要

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视注射的HCV抗体阴性人用于HCV感染的药物（PWID），并通过测试来识别和表征急性感染和再感染用于HCV RNA的血清和串行ALT和HCV RNA测试的血清转化。核心B的基础设施是在患有HCV感染风险的人中，完成HCV疫苗的首次试验所必需的，这将是有用的在未来的HCV疫苗试验中。血浆，血清和外周血单核细胞将是从感染之前，感染期间以及感染结果（清除或病毒以及在重新感染过程中的持久性。样本存储在存储库中以用于1-4个项目，以及其他HCV调查人员。核心B还将提供标准化的血清学测试以定量人类或接种动物的血浆或血清中的HCV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对于识别最有希望的疫苗至关重要候选人。通过将一组标准化的测定应用于疫苗接种后的样本和来自的人成功清除了多次HCV感染，我们将能够进行定量和定性的比较疫苗诱导的小鼠或非人类灵长类动物（项目3和5）的抗体反应与人类针对体内HCV的响应（项目2）。这将促进疫苗最大的识别进入人类试验后可能具有保护性。