Development of point-of-care testing for Lassa and other hemorrhagic fever arenaviruses

开发拉沙病毒和其他出血热沙粒病毒的即时检测

• 批准号: 10656548
• 负责人: MICHAEL D GUNN
• 金额: $ 39.7万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10656548
• 关键词: Address; Affinity; Africa; Animal Model; Antibodies; Antibody Affinity; Antigens; Archives; Arenavirus; Arenavirus Infections; Biological Assay; Blood; Bolivian Hemorrhagic Fever Virus; COVID-19; Caring; Case Fatality Rates; Categories; Category A pathogen; Cessation of life; Chapare Virus; Clinical; Clinical Sensitivity; Detection; Development; Diagnosis; Diagnostic; Diagnostic Reagent; Diagnostic Sensitivity; Disease; Disease Outbreaks; Ebola; Ebola virus; Emerging Communicable Diseases; Epidemic; Family; Future; Generations; Genetic Variation; Glycoproteins; Health; Human; Immunoassay; Infection; Junin virus; Laboratories; Lassa Fever; Lassa virus; Libraries; Lujo virus; Methods; Morbidity - disease rate; Nigeria; Patients; Phage Display; Primates; Printing; Procedures; Reader; Readiness; Reporting; Reverse Transcriptase Polymerase Chain Reaction; Risk; Sampling; Sensitivity and Specificity; Serum; Site; Source; Specificity; Technology; Testing; United States National Institutes of Health; Vaccines; Validation; Venezuelan hemorrhagic fever virus; Viral; Viral Hemorrhagic Fevers; Viral Proteins; Virus; Virus Diseases; Work; World Health Organization; Zoonoses; accurate diagnosis; antibody detection; antibody diagnostic; antibody libraries; assay development; bioweapon; diagnostic assay; diagnostic panel; diagnostic value; emerging pathogen; experience; global health; hemorrhagic fever virus; improved; member; mortality; novel; outbreak response; pandemic disease; pandemic potential; point of care; point of care testing; point-of-care diagnostics; priority pathogen; prospective; prototype; public health emergency; research and development; transmission process

Project Summary/Abstract Emerging infectious diseases pose a significant risk to human health. Among emerging pathogens, hemorrhagic fever viruses (HFVs) pose the greatest risk in terms of the potential for morbidity and mortality. These viruses are endemic in remote regions, produce large outbreaks that display high mortality rates, and have a high potential become pandemics. One of the largest families of HFVs is the Arenaviruses, which includes 6 DHHS select agents. The most well-known of these, Lassa virus, has caused an increasing number of infections in recent years, including a 2018 outbreak in Nigeria that led to over 100 deaths. In 2017, the World health Organization designated Lassa virus as a priority pathogen for R&D efforts due to its potential to generate a public health emergency. Other hemorrhagic fever arenaviruses, including Lujo, Chapare, Guanarito, Junin, and Machupo represent an increasing source of concern based on their increased distribution and recent instances of human-to-human transmission. Current diagnostic capabilities for Lassa virus and other arenaviruses are extremely limited, especially in the case of point-of-care (POC) diagnostic assays. Here, we propose to develop a POC diagnostic assay with the sensitivity and breadth of coverage required to diagnose Lassa virus infections currently present in West Africa. In addition, we will generate single chain antibody phage display libraries, broadly reactive high affinity diagnostic antibody pairs, a prototype assay chips for the 5 other arenaviruses that are Category A Priority Pathogens. We have previously used these procedures to develop a POC diagnostic assay for Ebola virus that displays a sensitivity better than the current gold standard, PCR. The successful completion of these studies will result in the first POC diagnostic assay that is capable of detecting all Lassa strains of clinical importance and a panel of high affinity diagnostic Abs and assays for all Category A Arenaviruses. In addition, the broadly reactive single chain antibody libraries we produce could be used to rapidly generate diagnostic antibodies against novel arenaviruses that arise as zoonotic outbreaks. This work will thus significantly improve our preparedness for almost any future major Arenavirus outbreak with pandemic potential.

项目概要/摘要 新出现的传染病对人类健康构成重大风险。在新出现的病原体中， 出血热病毒 (HFV) 在潜在的发病率和风险方面构成最大的风险 死亡。这些病毒在偏远地区流行，造成大规模爆发，表现出高 死亡率高，并且很有可能成为流行病。 HFV 最大的家族之一是 沙粒病毒，包括 6 种 DHHS 选择病毒。其中最著名的是拉沙病毒 近年来导致感染人数不断增加，其中包括 2018 年在尼日利亚爆发的疫情，导致 导致100多人死亡。 2017年，世界卫生组织将拉沙病毒列为重点防治对象 病原体用于研发工作，因为它有可能引发公共卫生紧急情况。其他出血性 发烧沙粒病毒，包括 Lujo、Chapare、Guanarito、Junin 和 Machupo 代表了越来越多的 由于其分布范围扩大和最近发生的人传人事件而令人担忧 传播。目前对拉沙病毒和其他沙粒病毒的诊断能力非常出色 有限，特别是在即时护理 (POC) 诊断分析的情况下。在此，我们建议开发一个 POC 诊断测定具有诊断拉沙病毒所需的灵敏度和覆盖范围 目前西非存在感染。此外，我们将生成单链抗体噬菌体 展示文库、广泛反应性高亲和力诊断抗体对、5 种原型检测芯片 其他属于 A 类优先病原体的沙粒病毒。我们之前使用过这些程序 开发一种埃博拉病毒 POC 诊断检测方法，其灵敏度优于目前的金检测方法 标准品，PCR。这些研究的成功完成将产生第一个 POC 诊断测定 能够检测所有具有临床重要性的拉沙病毒菌株和一组高亲和力诊断 所有 A 类沙粒病毒的 Abs 和检测。此外，具有广泛反应性的单链抗体 我们产生的文库可用于快速生成针对新型沙粒病毒的诊断抗体 作为人畜共患病爆发而出现。因此，这项工作将显着提高我们对几乎 未来任何具有大流行潜力的重大沙粒病毒爆发。