Inter-regional study of transmission, adaptation and pathogenesis of viruses with pandemic potential in Southeast Asia and West/Central Africa

对东南亚和西非/中非具有大流行潜力的病毒的传播、适应和发病机制进行区域间研究

• 批准号: 10219052
• 负责人: Anavaj SAKUNTABHAI
• 金额: $ 121.32万
• 依托单位: INSTITUT PASTEUR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-17 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10219052
• 关键词: Africa; Animals; Antibodies; Antibody Repertoire; Area; Arthropods; Biological; CD4 Positive T Lymphocytes; Cambodia; Cells; Cellular Immunity; Central Africa; Cloud Computing; Collection; Communicable Diseases; Computer Systems; Country; Crimean-Congo Hemorrhagic Fever Virus; Data Analyses; Dengue Virus; Diagnosis; Diagnostic; Diagnostic Reagent; Disease; Disease Outbreaks; Ebola; Emerging Communicable Diseases; Encephalitis; Endemic Diseases; Environment; Epidemic; Epidemiologist; Flavivirus; Future; Genome; Goals; Health; Healthcare; Healthcare Systems; Human; Immune response; Immunologic Receptors; Infection; Infectious Diseases Research; Infrastructure; Insect Vectors; Insecta; Knowledge; Laboratories; Molecular; Monoclonal Antibodies; Mutation; Outcome; Pathogenesis; Pharmaceutical Preparations; Phylogenetic Analysis; Population; Prevalence; Prevalence Study; RNA Viruses; Readiness; Reagent; Research Infrastructure; Rift Valley fever virus; Risk; Risk Factors; Role; Sampling; Senegal; Serology; Seroprevalences; Site; Southeastern Asia; Structure; Surveys; System; Technology; Variant; Viral; Viral Antibodies; Viral Hemorrhagic Fevers; Viral Pathogenesis; Virus; Virus Diseases; ZIKA; adaptive immune response; analysis pipeline; base; behavioral study; data sharing; design; detection method; efficacy study; emerging pathogen; high risk; human monoclonal antibodies; immunopathology; improved; insight; metagenomic sequencing; multiplex assay; novel; novel diagnostics; pandemic disease; pathogen; prevent; repository; response; reverse genetics; serosurvey; single-cell RNA sequencing; tool; transcriptomics; transmission process; vaccine development; vector; vector competence; virome

Project Summary/Abstract We will establish an Emerging Infectious Disease Research Center in Southeast Asia and West/Central Africa with an inter-continental one health approach designed to improve the capacity to respond rapidly and effectively to outbreaks. Our proposal is built on an existing network of laboratories/epidemiologists in close contact with national healthcare systems. We will identify factors influencing emergence and transmission at the virus, vector and reservoir level, leading to epidemics in suspected spillover conditions. We will focus on high priority RNA viruses with epidemic potential in Africa (Rift Valley Fever virus (RVFV), Crimean Congo Hemorrhagic Fever Virus (CCHFV)) and in Southeast Asia (dengue virus (DENV)) as well as viruses (Disease X) identified from symptomatic surveillance or insect sampling. We will tackle problems in emerging infectious diseases by the following specific aims: 1) Enhance surveillance and detect unknown RNA viruses with potential for spillover to humans. We will implement an autonomous solar-powered mobile suitcase laboratory for rapid pathogen identification in the field. Connection to a cloud computing system will facilitate data analysis and sharing among healthcare centers and laboratories. We will survey pathogens present in insects in different ecological settings. We will develop new diagnostic tools for these viruses and conduct prevalence and behavioral studies in human populations to determine risk factors. 2) Understand transmission dynamics of endemic RNA viruses with high risk of outbreak. We will focus on RVFV and CCHFV in Senegal and Cameroun, and DENV in Cambodia. We will perform surveys in animals and humans using a more specific multiplex assay. We aim at obtaining better knowledge on prevalence, transmission dynamics, and identifying major insect vectors and animal reservoirs. 3) Understand factors influencing adaptation of RNA viruses to new hosts. We will use state of the art technology to generate and study key candidate viral mutations using cells from relevant species including humans. We will study efficacy of these viruses in infection of various strains of insects to estimate transmission risks. This aim will lead to better understanding of the adaptation of these viruses to new hosts and will help design more detection methods. Lastly, 4) Study of host adaptive immune responses to emerging infectious diseases in South-East Asia and Africa. We will increase our insight into the adaptive immune response at a single cell level and the sequence-function relationship of human antibodies generated during infectious diseases (DENV, RVFV, CCHFV) by combining sequencing at a single cell level with antibody repertoire analysis. We will study function and characterize structure at a single antibody level. We will provide novel understanding of the role of cellular immunity in DENV disease. The proposed activity will allow the implementation of infrastructure and an analysis pipeline for outbreak preparedness in areas where viruses with potential pandemic threats circulate.

项目概要/摘要 我们将在东南亚和西/中建立新发传染病研究中心 非洲采用洲际单一卫生方法，旨在提高快速应对能力 并有效地控制疫情的爆发。我们的建议建立在现有的实验室/流行病学家网络的基础上 与国家医疗保健系统密切联系。我们将确定影响出现和出现的因素 病毒、媒介和储存库层面的传播，导致疑似溢出情况下的流行病。 我们将重点关注在非洲具有流行潜力的高优先级 RNA 病毒（裂谷热病毒 (RVFV)、 克里米亚刚果出血热病毒（CCHFV））和东南亚（登革热病毒（DENV）） 作为通过症状监测或昆虫采样鉴定出的病毒（疾病 X）。我们将解决问题 通过以下具体目标来应对新出现的传染病： 1) 加强监测和发现 可能传播给人类的未知 RNA 病毒。我们将实行自主 太阳能移动手提箱实验室，用于在现场快速识别病原体。连接到 云计算系统将促进医疗中心和实验室之间的数据分析和共享。 我们将调查不同生态环境中昆虫中存在的病原体。我们将开发新的诊断方法 针对这些病毒的工具，并在人群中进行患病率和行为研究，以确定 风险因素。 2) 了解具有高风险的地方性RNA病毒的传播动态 暴发。我们将重点关注塞内加尔和喀麦隆的 RVFV 和 CCHFV，以及柬埔寨的 DENV。我们将 使用更具体的多重检测对动物和人类进行调查。我们的目标是获得更好的 关于流行、传播动态以及识别主要昆虫媒介和动物的知识 水库。 3）了解影响RNA病毒适应新宿主的因素。我们将使用 使用来自相关细胞的最先进技术来生成和研究关键候选病毒突变 包括人类在内的物种。我们将研究这些病毒在感染各种昆虫品系中的功效，以 估计传播风险。这一目标将有助于更好地了解这些病毒的适应能力 新的主机并将有助于设计更多的检测方法。最后，4）宿主适应性免疫的研究 对东南亚和非洲新出现的传染病的应对措施。我们将增加我们的洞察力 研究单细胞水平的适应性免疫反应以及人类的序列功能关系 通过结合测序在传染病（DENV、RVFV、CCHFV）期间产生的抗体 单细胞水平的抗体库分析。我们将研究功能并表征结构 单一抗体水平。我们将对细胞免疫在登革热病毒疾病中的作用提供新的认识。 拟议的活动将允许实施基础设施和疫情分析渠道 在具有潜在大流行威胁的病毒传播地区做好准备。