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: 10650779
• 负责人: Anavaj SAKUNTABHAI
• 金额: $ 129.42万
• 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/10650779
• 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; Flavivirus; 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; Reaction; Reagent; Research Infrastructure; Rift Valley fever virus; Risk; Risk Factors; Role; Sampling; Senegal; Serology; Seroprevalences; Site; Solar Energy; Southeastern Asia; Structure; Surveys; System; Technology; Variant; Viral; Viral Antibodies; Viral Hemorrhagic Fevers; Viral Pathogenesis; Virus; Virus Diseases; ZIKA; adaptive immune response; analysis pipeline; behavioral study; data sharing; design; detection method; diagnostic tool; efficacy study; emerging pathogen; epidemic potential; future outbreak; high risk; human monoclonal antibodies; immunopathology; improved; insight; metagenomic sequencing; multiplex assay; novel; novel diagnostics; outbreak concern; outbreak preparedness; pandemic potential; 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.

项目摘要/摘要 我们将在东南亚和西/中心建立一个新兴的传染病研究中心 非洲具有洲际健康方法的非洲，旨在提高迅速反应的能力 并有效地爆发。我们的建议建立在现有的实验室/流行病学家网络上 与国家医疗保健系统密切联系。我们将确定影响出现的因素和 病毒，载体和储层水平的传播，导致可疑溢出条件下的流行病。 我们将重点关注非洲具有流行潜力的高优先率RNA病毒（Rift Valley Fever病毒（RVFV）， 克里米亚刚果出血病毒（CCHFV））和东南亚（登革热病毒（DENV）） 作为病毒（疾病X）从症状监测或昆虫采样中鉴定出来的。我们将解决问题 在新兴的传染病中通过以下特定目的：1）增强监视和检测 未知的RNA病毒，可能会向人类溢出。我们将实施自主 太阳能移动手提箱实验室，用于该领域的快速病原体鉴定。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 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病毒的传播动力学 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 使用更具体的多重测定法对动物和人进行调查。我们旨在获得更好的 了解患病率，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 使用来自相关的细胞生成和研究关键候选病毒突变的最先进技术 包括人类在内的物种。我们将研究这些病毒在各种昆虫菌株感染中的功效 估计传输风险。这个目标将使人们更好地理解这些病毒的适应 新主机将有助于设计更多检测方法。最后，4）研究宿主自适应免疫 对东南亚和非洲新兴传染病的反应。我们将增加洞察力 进入单个细胞水平的适应性免疫反应和人类的序列功能关系 在传染病（DENV，RVFV，CCHFV）期间产生的抗体，通过在A处结合测序 带有抗体库分析的单细胞水平。我们将研究功能和表征结构 单抗体水平。我们将对细胞免疫在DENV疾病中的作用提供新的了解。 拟议的活动将允许实施基础设施和爆发分析管道 在具有潜在大流行威胁的病毒流通的地区的准备。

项目成果

Resistance of Omicron subvariants BA.2.75.2, BA.4.6, and BQ.1.1 to neutralizing antibodies.

• DOI: 10.1038/s41467-023-36561-6
• 发表时间: 2023-02-14
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Planas, Delphine;Bruel, Timothee;Staropoli, Isabelle;Guivel-Benhassine, Florence;Porrot, Francoise;Maes, Piet;Grzelak, Ludivine;Prot, Matthieu;Mougari, Said;Planchais, Cyril;Puech, Julien;Saliba, Madelina;Sahraoui, Riwan;Femy, Florent;Morel, Nathalie;Dufloo, Jeremy;Sanjuan, Rafael;Mouquet, Hugo;Andre, Emmanuel;Hocqueloux, Laurent;Simon-Loriere, Etienne;Veyer, David;Prazuck, Thierry;Pere, Helene;Schwartz, Olivier
• 通讯作者: Schwartz, Olivier

Resistance of Omicron subvariants BA.2.75.2, BA.4.6 and BQ.1.1 to neutralizing antibodies.

• DOI: 10.1101/2022.11.17.516888
• 发表时间: 2022-11-21
• 期刊: bioRxiv : the preprint server for biology
• 作者: Planas, Delphine;Bruel, Timothee;Schwartz, Olivier
• 通讯作者: Schwartz, Olivier

Untargeted metagenomic sequencing identifies Toscana virus in patients with idiopathic meningitis, southern Spain, 2015 to 2019.

• DOI: 10.2807/1560-7917.es.2023.28.45.2200913
• 发表时间: 2023-11
• 期刊: Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin

Aerosol exposure of live bird market workers to viable influenza A/H5N1 and A/H9N2 viruses, Cambodia.

• DOI: 10.1111/zph.13009
• 发表时间: 2023-03
• 期刊: ZOONOSES AND PUBLIC HEALTH
• 影响因子: 2.4
• 作者: Horwood, Paul F.;Horm, Srey Viseth;Yann, Sokhoun;Tok, Songha;Chan, Malen;Suttie, Annika;Phalla, Y.;Rith, Sareth;Siegers, Jurre Y.;San, Sorn;Davun, Holl;Tum, Sothyra;Ly, Sowath;Tarantola, Arnaud;Dussart, Philippe;Karlsson, Erik A.
• 通讯作者: Karlsson, Erik A.

Longitudinal Study of Viral Diversity Associated with Mosquito Species Circulating in Cambodia.

• DOI: 10.3390/v15091831
• 发表时间: 2023-08-29
• 期刊: Viruses
• 作者: Mohamed Ali S;Rakotonirina A;Heng K;Jacquemet E;Volant S;Temmam S;Boyer S;Eloit M
• 通讯作者: Eloit M