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: 10393616
• 负责人: NAGLAA H. SHOUKRY
• 金额: $ 40.81万
• 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/10393616
• 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; vaccine response

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 摘要 丙型肝炎病毒（HCV）是一种感染肝脏的病毒，通过受污染的血液传播。HCV 感染仍然是公共卫生的优先事项，也是世界范围内肝病的主要原因，特别是在发展中国家， 像埃及这样的国家新的HCV感染在北美也在增加，与阿片类药物有关 疫情虽然新的抗病毒药物可以治愈超过95%的感染者，但许多人并不知道他们是 感染并保持发展为肝病的风险和新感染的活跃来源。此外，委员会认为， 如果个体再次暴露于病毒，成功的治疗不能防止再次感染。因此，有一个 我们迫切需要能够预防这种病毒的疫苗。不幸的是，尽管我们知道 针对HCV的免疫反应，我们仍然没有有效的疫苗。唯一一种疫苗的最新结果 进入大规模（2期）临床试验的候选药物在注射的人中没有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， 保护能够自发清除病毒的患者群体免受HCV感染。这个的主要目标 建议是确定这些因素是必不可少的，以实现保护性免疫。该临床核心的目的是 是监督和管理两组感染HCV的受试者，以定义这些保护性免疫 因素第一个队列位于蒙特利尔，是一群注射毒品的人， 两次HCV感染，我们想在疫苗中模拟这种反应。本队列 已经成立（15年），将在整个项目中招募新的受试者，并已经储存了样本 从许多再感染病例中解脱出来，立即启动项目。它还将包括一个较小的PWID子队列， 主要感染基因型1和3，正在接受抗病毒治疗。第二个是一个大的队列， 来自埃及的接受HCV抗病毒治疗的个体，埃及是HCV感染人数最多的国家。 感染世界。这第二个队列主要感染基因型4，将使我们了解 使用抗病毒治疗治愈HCV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和有关疾病进展和病毒的临床数据， 珍贵的队列，我们将能够研究HCV特异性免疫反应，并确定免疫因素 应该成为新型疫苗的目标。