GH19-003, Epidemiology and Immunity to Ebola Virus and Other Emerging Viral Infections in Liberia

项目总结 利比里亚是一个资源丰富但经济贫穷的国家，在下列情况下继续与增长和复苏作斗争 长达14年的内战摧毁了它的基础设施。2014-16年的埃博拉病毒病(EVD)疫情 对西非的破坏性影响导致10,678例疑似、可能和确诊病例以及4,810例 利比里亚的死亡人数。由于并非所有感染埃博拉病毒(EBOV)的人都寻求医疗救治或接受治疗 实验室确认埃博拉病毒病后，疫情的全部规模仍不得而知。而西非 疫情的爆发促进了对自然历史、社会行为背景和 埃博拉病毒应对措施的有效性，人们对埃博拉病毒后遗症的认识仍然存在很大差距， 对埃博拉病毒感染和疾病的免疫反应，以及随着时间的推移免疫的持久性。另一个主题 令人担忧的是，埃博拉病毒在埃博拉病毒幸存者的免疫保护部位持续存在(可能 未诊断的埃博拉病毒感染)。持续感染导致病毒的性传播和 在广泛传播结束后，随后出现的疾病集群。这种病毒的持久性结合在一起 对埃博拉病毒和其他流行病毒的血清流行病学监测数据极少 西非的潜在风险构成了埃博拉病毒感染或疾病病例死灰复燃的持续风险， 以前报告或未发现的新聚集性或大规模暴发的可能性 感染。根据疾控中心的使命，这个项目的目的是建立一个血清学基线 未来的监测平台，允许研究潜在的病因、特征和反应 新出现的感染。这将促进我们对优先流行的易感病毒疾病的综合了解 利比里亚允许制定预防未来疫情的战略，通过将常规、 有针对性的血清监测和疾病及干预模型。 我们建议通过以下四个具体目标来解决总体研究目标：(1)开发和 优化病毒特异性抗体检测方法。检测抗体反应的多重免疫分析方法 对相关病毒抗原将进一步提纯。(2)建立记录细胞免疫的检测方法 人类对新出现的病毒病原体的反应。埃博拉和埃博拉幸存者的细胞免疫 将使用流式细胞术和转录组分析来记录拉萨病毒感染情况，以开发一种 这些感染的免疫学特征。(3)确定埃博拉病毒证据的血清学基线 以及利比里亚各地的其他新出现的病毒感染。利比里亚所有卫生区的样本将是 收集并分析以前感染过病毒的证据。(4)对免疫力进行时序评估 年有症状和无症状的埃博拉和拉萨病毒幸存者的状况和相关健康结局 与血清阴性人群相比。跟随之前感染过EBOV或 拉萨病毒将允许建立对这些优先病原体的免疫力减弱的时间进程。

PROJECT SUMMARY Liberia, a resource rich but economically poor country, continues to struggle with growth and recovery following a 14-year civil war that destroyed its infrastructure. The 2014-16 Ebola Virus Disease (EVD) epidemic had a devastating impact in West Africa resulting in 10,678 suspected, probable and confirmed cases and 4,810 deaths in Liberia. As not all individuals infected with Ebola virus (EBOV) sought medical attention or received laboratory confirmation of EVD, the full magnitude of the outbreak is still unknown. While the West African outbreak permitted advancement of scientific inquiry into the natural history, sociobehaviorial context, and effectiveness of countermeasures for EVD, significant gaps in knowledge remain about post-Ebola sequelae, immune responses to Ebola virus infection and disease, and durability of immunity over time. Another subject of concern is the persistence of EBOV in immunologically protected sites of EVD survivors (and potentially undiagnosed Ebola virus infections). Persistent infection has resulted in sexual transmission of the virus and subsequent clusters of disease following the end of widespread transmission. This viral persistence combined with minimal available seroepidemiological surveillance data for Ebola and other viruses with epidemic potential in West Africa poses a continued risk for resurgence of Ebola virus infection or disease cases and the possibility of new clusters or large-scale outbreaks originating from previously reported or unrecognized infections. In line with the mission of CDC, this project is aimed at establishing a serological baseline for a future surveillance platform, allowing the study of underlying etiologies, characteristics, and response to emerging infections. This will advance our combined knowledge on priority epidemic-prone viral diseases in Liberia, allowing development of strategies to prevent future outbreaks through a combination of conventional, targeted serosurveillance and disease and intervention modeling. We propose to address the overall research goals with the following four Specific Aims: (1) Develop and optimize virus-specific antibody-detection assays. Multiplex immunoassays for detection of antibody responses to relevant viral antigens will be further refined. (2) Establish assays to document cell-mediated immune responses in humans against emerging viral pathogens. Cell-mediated immunity in survivors of Ebola and Lassa virus infections will be documented using flow cytometry and transcriptome analysis to develop an immunological signature for these infections. (3) Determine a serological baseline of evidence of Ebola virus and other emerging viral infections throughout Liberia. Samples from all health districts in Liberia will be collected and analyzed for evidence of prior viral infections. (4) Conduct temporal assessment of the immune status and associated health outcomes in Ebola and Lassa virus symptomatic and asymptomatic survivors in comparison to the seronegative population. Following cohorts of persons previously infected with EBOV or Lassa virus will allow establishment of a time course for waning immunity to these priority pathogens.