Correlates of protective immunity to HCV and rational vaccine design: Clinical Core

HCV 保护性免疫与合理疫苗设计的相关性：临床核心

• 批准号: 10205766
• 负责人: NAGLAA H. SHOUKRY
• 金额: $ 24.06万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-15 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10205766
• 关键词: Acute; American; Antiviral Agents; Antiviral Therapy; Blood; Blood specimen; Cells; Chronic; Clinical; Clinical Data; Collaborations; Country; Databases; Developing Countries; Development; Diagnosis; Disease Progression; Egypt; Exposure to; Future; Genotype; Goals; Hepatitis C; Hepatitis C Prevalence; Hepatitis C Vaccine; Hepatitis C virus; High Prevalence; Human Resources; Immune; Immune response; Immunity; Immunologic Factors; Income; Individual; Infection; Injecting drug user; Injections; International; Knowledge; Laboratories; Life; Liver; Liver diseases; Measures; Mediating; Medical; Modeling; North America; Patients; Persons; Phase; Phase II Clinical Trials; Populations at Risk; Pre-Clinical Model; Procedures; Process; Public Health; Research; Research Personnel; Rest; Risk; Sampling; Source; Specimen; T-Lymphocyte; Time; Training; Vaccine Design; Vaccines; Virus; base; biobank; chronic infection; chronic liver disease; cohort; experience; experimental study; follow-up; healthy volunteer; high risk; high risk population; immunogenic; immunogenicity; infection risk; injection drug use; novel vaccines; opioid epidemic; phase II trial; prevent; public health priorities; reconstitution; recruit; response; screening; seropositive; success; vaccine candidate; vaccine evaluation

Core B: Clinical Core Abstract Hepatitis C virus (HCV) is a virus that infects the liver and is transmitted through contaminated blood. HCV infection is still a public health priority and a major cause of liver disease worldwide, especially in developing countries like Egypt. New HCV infections are also on the rise in North America in association with the opioid epidemic. While new antiviral drug can cure >95% of infected individuals, many do not know that they are infected and remain at risk of developing liver disease and an active source of new infections. Furthermore, successful treatment does not prevent reinfection if the individual is re-exposed to the virus. Hence, there is an urgent need for vaccines that can protect against this virus. Unfortunately, despite our knowledge about the immune response against HCV, we still do not have an effective vaccine. Recent results from the only vaccine candidate that made it into a large scale (Phase 2) clinical trial did not show any protection in people who inject drugs at risk of HCV infection. This means that we need to understand better the immune factors and cells that protect against HCV in cohorts of patients who are able to clear the virus spontaneously. The main goal of this proposal is to define these factors that are essential to achieve protective immunity. The aim of this clinical core is to oversee and manage two cohorts of subjects that are infected with HCV to define these protective immune factors. The first cohort is located in Montreal and is a cohort of people who inject drugs who were able to clear two subsequent infections with HCV, a response that we would like to simulate in a vaccine. This cohort is already established (15 years), will recruit new subjects throughout the project and already has banked samples from many reinfection cases to start the projects right away. It will also include a smaller subcohort of PWID, primarily infected with genotypes 1 and 3, undergoing antiviral treatment. The second is a large cohort of individuals undergoing antiviral therapy for HCV from Egypt, the country with the highest number of HCV infections in the world. This second cohort is primarily infected with genotype 4 and will allow us to understand whether curing HCV infection using antiviral treatments will enhance these protective immune factors and cells. By collecting well defined blood samples and clinical data about disease progression and virus from these precious cohorts, we will be able to study the HCV-specific immune response and identify the immune factors that should be targeted in novel vaccines.

核心 B：临床核心 抽象的 丙型肝炎病毒（HCV）是一种感染肝脏并通过受污染的血液传播的病毒。丙型肝炎病毒 感染仍然是一个公共卫生优先事项，也是全世界肝病的主要原因，特别是在发展中国家 埃及等国家。北美与阿片类药物相关的新发丙肝病毒感染也在增加 流行性。虽然新的抗病毒药物可以治愈 > 95% 的感染者，但许多人并不知道它们是 已感染并仍面临患肝病的风险，并且是新感染的活跃来源。此外， 如果个体再次接触病毒，成功的治疗并不能防止再次感染。因此，有一个 迫切需要能够预防这种病毒的疫苗。不幸的是，尽管我们了解 针对HCV的免疫反应，我们仍然没有有效的疫苗。唯一疫苗的最新结果 进入大规模（第二阶段）临床试验的候选药物并未对注射者显示出任何保护作用 有 HCV 感染风险的药物。这意味着我们需要更好地了解免疫因子和细胞 在能够自发清除病毒的患者群体中预防丙肝病毒。此次活动的主要目标 建议定义这些对于实现保护性免疫至关重要的因素。该临床核心的目标 是监督和管理两组感染 HCV 的受试者，以确定这些保护性免疫 因素。第一个队列位于蒙特利尔，是一组注射毒品的人，他们能够清除 随后两次感染 HCV，我们希望在疫苗中模拟这种反应。这个队列是 已经成立（15年），将在整个项目中招募新受试者，并且已经储存了样本 从许多再感染病例中立即启动项目。它还将包括一个较小的注射吸毒者子群体， 主要感染基因型1和3，正在接受抗病毒治疗。第二个是一大群 来自埃及（HCV 数量最多的国家）接受 HCV 抗病毒治疗的个人 世界各地的感染情况。第二组主要感染基因型 4，这将使我们能够了解 使用抗病毒治疗治愈丙型肝炎病毒感染是否会增强这些保护性免疫因子和细胞。 通过收集明确的血液样本以及有关疾病进展和病毒的临床数据 宝贵的队列，我们​​将能够研究 HCV 特异性免疫反应并识别免疫因素 新型疫苗应针对这一点。