Development of Rapid Diagnostic Tests for Hantaviruses

汉坦病毒快速诊断测试的开发

• 批准号: 7169822
• 负责人: Sergio Pichuantes
• 金额: $ 96.47万
• 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/7169822
• 关键词: Animal Model; Antibodies; Biological Assay; Bioterrorism; Blood; Breeding; Cardiopulmonary; Cell surface; Clinical; Collaborations; Complementary RNA; Deer Mouse; Detection; Development; Diagnosis; Diagnostic; Diagnostic tests; Diagnostics Research; Disease Outbreaks; Dose; Early Diagnosis; Epidemiologist; Evaluation; Exhibits; Flow Cytometry; Funding; Genetic Transcription; Genomics; Genotype; Hantavirus; Hantavirus Infections; Haplotypes; Hospitalization; Hour; Human; Immune response; Immunoglobulin G; Immunoglobulin M; Inbreeding; Individual; Infection; Major Histocompatibility Complex; Medical; Messenger RNA; Methodology; Methods; Modality; Mus; New Mexico; Nucleic Acids; Pathogenesis; Pathogenicity; Patients; Peripheral Blood Mononuclear Cell; Plasma; Population; Prevention; Production; Public Health; Purpose; RNA; Reagent; Research; Research Personnel; Research Proposals; Rodent; Role; Sampling; Scientist; Sensitivity and Specificity; Serum; Severity of illness; Siblings; Sin Nombre virus; Speed; Symptoms; Syndrome; Technology; Testing; Time; Universities; Variant; Viral; Viral Antigens; Viral Hemorrhagic Fevers; Viral Load result; Virus; Virus Diseases; Work; base; cell mediated immune response; chiron vaccine; cytokine; follow-up; health organization; improved; medical schools; programs; tissue culture; tool; viral RNA

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、易于使用的核酸诊断试验，以检测汉坦病毒感染者和携带啮齿动物的血液、血浆或血清中的汉坦病毒；(2)开发一种快速诊断试验，以检测感染者血液、血浆或血清中的汉坦病毒抗体；(3)开发汉坦病毒核酸鉴别试验；(4)开发基于taqman的定量分析方法，以估计病毒感染样本中的汉坦病毒载量。(5)建立汉坦病毒心肺综合征（HCPS）患者外周血单个核细胞（PBMC）中Sin Nombre病毒（SNV）抗原的流式细胞术检测方法；(6)建立全纯合鹿小鼠近交系亚系；(7)建立分析鹿小鼠对汉坦病毒感染的细胞免疫反应的工具。汉坦病毒核酸和抗体诊断测试应能够在不到一小时内产生结果，并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允许鉴定与汉坦病毒暴发有关的特定病毒分离株及其可能的来源。准确定量汉坦病毒在人类患者或动物模型中的载量的方法，以及基于流式细胞术的SNV检测、近交纯合子鹿小鼠的可用性，以及解剖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、预防和治疗汉坦病毒感染。这项研究涉及凯龙公司和新墨西哥大学医学院的合作努力。这两个组织以前的合作始于1994年，但1997年停止，当时凯龙公司撤回了对汉坦病毒诊断研究的资助，因为当时没有战略上的契合。本任务中提出的研究所产生的信息对于迅速查明可能涉及汉坦病毒制剂的生物恐怖主义袭击至关重要，对于协助医疗和公共卫生组织有效应对汉坦病毒爆发和/或威胁至关重要。

项目成果

Recognition of decay accelerating factor and alpha(v)beta(3) by inactivated hantaviruses: Toward the development of high-throughput screening flow cytometry assays.

• DOI: 10.1016/j.ab.2010.03.016
• 发表时间: 2010-07-15
• 期刊: Analytical biochemistry
• 影响因子: 2.9
• 作者: Buranda T;Wu Y;Perez D;Jett SD;BonduHawkins V;Ye C;Edwards B;Hall P;Larson RS;Lopez GP;Sklar LA;Hjelle B
• 通讯作者: Hjelle B