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

项目摘要 利比里亚是一个资源丰富但经济贫穷的国家， 长达14年的内战摧毁了基础设施2014-16年埃博拉病毒病（EVD）疫情发生在 在西非造成了破坏性影响，导致10 678例疑似、可能和确诊病例， 死亡在利比里亚由于并非所有感染埃博拉病毒（EBOV）的人都寻求医疗照顾或获得 尽管实验室证实了埃博拉病毒病，但疫情的整体规模仍不清楚。虽然西非 爆发允许推进科学调查的自然历史，社会行为背景， EVD对策的有效性，对埃博拉后遗症的认识仍然存在重大差距， 对埃博拉病毒感染和疾病的免疫反应，以及免疫力随时间的持久性。另一个主题 值得关注的是EBOV在EVD幸存者的免疫保护部位的持续存在（并且可能 未确诊的埃博拉病毒感染）。持续感染导致病毒的性传播， 大范围传播结束后的后续疾病集群。这种病毒的持久性 埃博拉和其他流行性病毒的血清流行病学监测数据极少， 西非潜在的埃博拉病毒感染或疾病病例重新出现的持续风险， 新的聚集性或大规模暴发的可能性源自先前报告或未识别的 感染.根据疾病预防控制中心的使命，本项目旨在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、特征和对 新出现的感染这将促进我们对优先的易感染病毒性疾病的综合认识， 利比里亚，允许制定战略，通过常规、 有针对性的血清监测以及疾病和干预建模。 我们提出的总体研究目标有以下四个具体目标：（1）开发和 优化病毒特异性抗体检测分析。用于检测抗体应答的多重免疫测定 与相关病毒抗原的关系将进一步完善。(2)建立检测方法以记录细胞介导的免疫 人类对新出现的病毒病原体的反应。埃博拉病毒幸存者的细胞介导免疫， 将使用流式细胞术和转录组分析来记录拉沙病毒感染，以开发一种新的病毒检测方法。 这些感染的免疫特征(3)确定埃博拉病毒证据的血清学基线 和其他新出现的病毒感染。将从利比里亚所有卫生区采集样本， 收集并分析先前病毒感染的证据。(4)进行免疫的时间评估 埃博拉和拉沙病毒有症状和无症状幸存者的状况和相关健康结果 与血清阴性人群相比。在先前感染EBOV或 拉沙病毒将允许建立对这些优先病原体的免疫力减弱的时间过程。

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.