Development of Rapid Diagnostic Tests for Hantaviruses

汉坦病毒快速诊断测试的开发

• 批准号: 6847409
• 负责人: Sergio Pichuantes
• 金额: $ 106.03万
• 依托单位: NOVARTIS VACCINES AND DIAGNOSTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-15 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6847409
• 关键词: Hantavirus; Peromyscus; Sin Nombre virus; animal breeding; biotechnology; bioterrorism /chemical warfare; cellular immunity; clinical research; communicable disease diagnosis; cooperative study; diagnosis design /evaluation; diagnostic tests; flow cytometry; genotype; human subject; immunoglobulin G; immunoglobulin M; major histocompatibility complex; nucleic acid quantitation /detection; patient oriented research; rapid diagnosis; serology /serodiagnosis; virus RNA; virus antigen; virus infection mechanism; virus load

DESCRIPTION (provided by applicant): The objectives of this research proposal are (1) to develop a rapid and easy-to-use nucleic acid diagnostic test to detect hantaviruses in blood, plasma, or serum of infected individuals and carrier rodents, (2) to develop a rapid diagnostic test to detect hantavirus antibodies in blood, plasma, or serum of infected individuals, (3) to develop a hantavirus nucleic acid discriminatory test, (4) to develop TaqMan-based quantitative assays to estimate hantavirus load in virus infected samples, (5) to develop a flow cytometry assay to detect Sin Nombre virus (SNV) antigen in peripheral blood mononuclear cells (PBMC) of patients with hantavirus cardiopulmonary syndrome (HCPS), (6) to develop inbred sublines of fully homozygous deer mice, and (7) to establish tools to dissect deer mouse cellular immune responses to hantavirus infection. The hantavirus nucleic acid and antibody diagnostic tests should be able to yield results in less than one hour, and will assist in the early detection and follow up of hantavirus infections. The availability of the hantavirus nucleic acid discriminatory assay will allow identification of specific viral isolates involved in hantavirus outbreaks and their possible origins. Methods to accurately quantitate hantavirus load in human patients or in animal models, along with the availability of a flow cytometry-based SNV assay, inbred homozygous deer mice, and methodologies to dissect the deer mouse cellular immune responses to hantavirus will facilitate better understanding, prevention, and treatment of hantavirus infections. This research involves collaborative efforts between Chiron Corporation and the School of Medicine, University of New Mexico. A previous collaboration between the two organizations was initiated in 1994 but discontinued in 1997 when Chiron Corporation withdrew funding for hantavirus diagnostic research, as there was no strategic fit at that time. The information generated from the studies proposed in this task will be crucial for the rapid identification of possible bioterrorism attacks involving hantavirus agents and will be vital to assist the medical and public health organizations to efficiently respond to hantavirus outbreaks and/or threats.

描述（由申请人提供）：本研究计划的目标是 (1) 开发一种快速且易于使用的核酸诊断测试，以检测受感染个体和带菌啮齿动物的血液、血浆或血清中的汉坦病毒，(2 ) 开发快速诊断测试来检测感染个体的血液、血浆或血清中的汉坦病毒抗体，(3) 开发汉坦病毒核酸区分测试，(4) 开发基于 TaqMan 的定量测定法来估计汉坦病毒载量病毒感染的样本，(5) 开发流式细胞术检测汉坦病毒心肺综合征 (HCPS) 患者外周血单核细胞 (PBMC) 中的 Sin Nombre 病毒 (SNV) 抗原，(6) 开发完全纯合的近交亚系鹿小鼠，以及（7）建立工具来剖析鹿小鼠对汉坦病毒感染的细胞免疫反应。汉坦病毒核酸和抗体诊断检测应能在不到一小时内得出结果，将有助于汉坦病毒感染的早期发现和随访。汉坦病毒核酸鉴别测定的可用性将有助于鉴定参与汉坦病毒爆发的特定病毒分离株及其可能的起源。准确定量人类患者或动物模型中汉坦病毒载量的方法，以及基于流式细胞术的 SNV 检测、近交纯合鹿小鼠以及剖析鹿小鼠对汉坦病毒的细胞免疫反应的方法，将有助于更好地理解和预防和汉坦病毒感染的治疗。这项研究涉及 Chiron 公司和新墨西哥大学医学院的合作。两个组织之前的合作始于 1994 年，但由于当时没有战略契合，Chiron 公司撤回了对汉坦病毒诊断研究的资助，因此于 1997 年终止。本任务中提出的研究产生的信息对于快速识别涉及汉坦病毒制剂的可能的生物恐怖袭击至关重要，并且对于协助医疗和公共卫生组织有效应对汉坦病毒爆发和/或威胁也至关重要。