The Protective and Pathologic Features of the EVD Survivor Immune System

埃博拉病毒病幸存者免疫系统的保护和病理特征

基本信息

批准号：
10639583
负责人：
William Fischer
金额：
$ 71.59万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-05-09 至 2028-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10639583
关键词：
Activities of Daily Living Acute Address Africa African Age Animal Model Antibodies Area Attention Autoantibodies Autoimmune Autoimmunity Caring Central Africa Chiroptera Clinical Clinical Management Clinical Research Cohort Studies Communicable Diseases Country Data Decision Making Democratic Republic of the Congo Detection Disease Disease Outbreaks Ebola Ebola Hemorrhagic Fever Ebola virus Enrollment Ensure Epidemic Evaluation Filovirus Frequencies Fright Guinea Healthcare Household Human Humoral Immunities Immune Immune response Immune system Immunity Immunologic Memory Immunology Infection Inflammation Investigation Kinetics Knowledge Left Liberia Link Longevity Longitudinal cohort Measures Memory Memory B-Lymphocyte Mus Musculoskeletal Neurologic Pathogenesis Pathogenicity Pathologic Persons Plasma Public Health Recording of previous events Recurrence Reporting Research Infrastructure Role Sampling Serology Sierra Leone Survivors Sushi Domain Symptoms Therapeutic Intervention Time Vaccination Viral Viremia Virus Virus Diseases Work acute infection clinical implementation clinical infrastructure cohort ds-DNA future epidemic future outbreak immune activation improved insight multidisciplinary neutralizing antibody nonhuman primate pathogen personal protective equipment post intervention previous outbreak prospective public health relevance recruit response sex symptomatology viral outbreak

项目摘要

In the more than 40 years since the discovery of the Ebola virus (EBOV) there has been an increase in both the frequency, size, and duration of Ebola outbreaks. The 2014-2016 outbreak that devastated West Africa evolved within the span of months into a global humanitarian crisis, infecting over 28,600 people and killing more than 11,300 - eclipsing all previous outbreaks combined. Moreover, in the six years since the end of the West African Ebola epidemic, there have been seven additional outbreaks in Guinea and the Democratic Republic of Congo (DRC). The recurrence of Ebola in Guinea and the DRC and the detection of the Ebola virus in a bat in Liberia, make it clear that this pathogen is persistent and will be the cause of recurrent outbreaks of varying scales across West and Central Africa. While the West African epidemic has ended, the clinical concerns of EVD survivors persist including the longevity of immune protection against repeat infection and the mechanisms underlying the persistent and debilitating somatic complaints reported by an overwhelming majority. The primary objective of this proposal is a rigorous characterization of the protective and pathologic effects of the EVD survivor immune response in one of the largest EVD survivor cohorts. Specifically: • AIM I will characterize the humoral immune response to EBOV infection by measuring antibody levels and neutralizing capacity - a key correlate of protection, and assessing the memory immune response in seronegative EVD survivors from 1 to 10 years following acute infection • AIM II will investigate autoimmune activation as a mechanism underlying post-Ebola complications We will conduct this work in the context of close and strong working relationships with healthcare leaders and Ebola survivor representatives in West Africa, and well-developed infrastructure for clinical research that we have established in Liberia and Sierra Leone where we have recruited, enrolled, and longitudinally followed and sampled more than 700 EVD survivors and over 1,000 household contacts. The proposed work will provide a much-needed longitudinal characterization of the humoral immune response, evaluation of the memory immune response to EBOV infection, and investigation of autoimmune activation as a mechanism underlying the long- term complications of surviving EVD. With seven outbreaks, including the second largest Ebola outbreak ever, occurring in the 6 years since the West African epidemic, the question is not if another large outbreak will occur but when. This study will ensure that the world is better prepared for the next epidemic through an improved understanding of the durability of the humoral immune response to infection, an improved understanding of the clinical complications of EVD, and through the implementation of clinical research platforms in areas that are likely to see a recurrence of EVD.

自发现埃博拉病毒 (EBOV) 以来的 40 多年来，埃博拉疫情爆发的频率、规模和持续时间均有所增加，2014 年至 2016 年肆虐西非的埃博拉疫情在短短几个月内就爆发了。一场全球人道主义危机，导致 28,600 多人感染，11,300 多人死亡——超过了西方灭亡以来的六年内所有疫情爆发的总和。非洲埃博拉疫情，几内亚和刚果民主共和国又出现7起埃博拉疫情，几内亚和刚果民主共和国再次出现埃博拉病毒，以及利比里亚一只蝙蝠中检测到埃博拉病毒，表明这种病原体。尽管西非疫情已经结束，但埃博拉病毒病幸存者的临床担忧仍然存在，包括针对重复感染的免疫保护的寿命以及持续存在的机制。该提案的主要目标是对最大的埃博拉病毒病幸存者群体之一的埃博拉病毒病幸存者免疫反应的保护性和病理性影响进行严格表征。 • AIM I 将通过测量抗体水平和中和能力（保护的关键相关性）来表征针对 EBOV 感染的体液免疫反应，并评估急性感染后 1 至 10 年内血清阴性 EVD 幸存者的免疫记忆反应 • AIM II 将研究自身免疫激活作为埃博拉后并发症的潜在机制我们将在与西非医疗保健领导者和埃博拉幸存者代表密切而牢固的工作关系以及我们在利比里亚和塞拉利昂建立的完善的临床研究基础设施的背景下开展这项工作，我们在利比里亚和塞拉利昂招募、登记和对 700 多名埃博拉病毒病幸存者和 1,000 多名家庭接触者进行了纵向跟踪和采样。拟议的工作将提供急需的体液免疫反应的纵向特征、对 EBOV 感染的记忆免疫反应的评估以及自身免疫的调查。自西非疫情爆发以来的六年内，发生了七次埃博拉疫情，其中包括有史以来第二大埃博拉疫情，问题不在于是否会发生另一次大规模疫情，而在于何时发生。这项研究将通过更好地了解对感染的体液免疫反应的持久性、更好地了解埃博拉病毒病的临床并发症以及通过在以下领域实施临床研究平台，确保世界为下一次流行病做好更好的准备：是可能会出现埃博拉病毒病复发。