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.

项目摘要/摘要 新兴的传染病对人类健康构成了重大风险。在新兴的病原体中， 出血性发烧病毒（HFVS）在发病率和 死亡。这些病毒在偏远地区是地方性的，产生大型暴发，显示高 死亡率，并且具有很高的潜力成为大流行病。 HFV的最大家族之一是 体育症病毒，其中包括6个DHHS精选代理。其中最著名的Lassa病毒具有 近年来引起越来越多的感染，其中包括2018年在尼日利亚爆发 超过100人死亡。 2017年，世界卫生组织将LASSA病毒指定为优先事项 研发努力的病原体由于可能产生公共卫生紧急情况。其他出血 发烧体轨道病毒，包括Lujo，Chapare，Guanarito，Junin和Machupo，代表着越来越多的 基于他们的分布增加和人类对人类的最新实例的关注来源 传播。 LASSA病毒和其他体育症病毒的当前诊断能力极为 有限，特别是在护理点（POC）诊断测定的情况下。在这里，我们建议开发 POC诊断测定法具有诊断LASSA病毒所需的覆盖范围的灵敏度和宽度 目前在西非出现感染。此外，我们将生成单链抗体噬菌体 显示库，广泛反应性的高亲和力诊断抗体对，一种原型测定芯片5 其他属于类别的竞技病毒病原体。我们以前已经使用了这些程序 为埃博拉病毒开发POC诊断测定法，该测定法比当前的黄金更好地显示灵敏度 标准，PCR。这些研究的成功完成将导致第一个POC诊断测定 能够检测所有临床重要性的LASSA菌株和高亲和力诊断的面板 ABS和ARANAVIRES所有类别的ABS和测定。另外，广泛反应性的单链抗体 我们生产的图书馆可用于快速生成针对新型体属病毒的诊断抗体 这是人畜共患爆发。因此，这项工作将显着改善我们的准备 任何未来的重大体育症病毒爆发都具有大流行潜力。