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: 10428559
• 负责人: Anavaj SAKUNTABHAI
• 金额: $ 128.71万
• 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/10428559
• 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 Reagent; Disease; Disease Outbreaks; Ebola; Emerging Communicable Diseases; Encephalitis; Endemic Diseases; Environment; Epidemic; Epidemiologist; Far East; 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; diagnostic tool; 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.

项目总结/文摘