Rapid antigen detection test for Dengue infection

登革热感染快速抗原检测测试

• 批准号: 7272941
• 负责人: Raymond Houghton
• 金额: $ 37.5万
• 依托单位: INBIOS INTERNATIONAL, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-15 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7272941
• 关键词: Acute; Address; Antibodies; Antigen Targeting; Antigens; Area; Biological Assay; Bioterrorism; Biotin; Categories; Class; Clinical; Culicidae; Decision Making; Dengue; Dengue Hemorrhagic Fever; Dengue Virus; Detection; Development; Devices; Diagnosis; Diagnostic; Disease; Disease Outbreaks; Early Diagnosis; Early identification; Enzyme-Linked Immunosorbent Assay; Equipment; Evaluation; Family; Fever; Flaviviridae; Flavivirus; Fluorescence; Goals; Hand; Hawaii; Human; Immune Sera; Immunoassay; Immunoglobulin G; Immunoglobulin M; Individual; Infection; International; Japanese Encephalitis; Label; Lateral; Lead; Life; Monitor; Monoclonal Antibodies; National Institute of Allergy and Infectious Disease; Numbers; Patients; Performance; Phase; Polymerase Chain Reaction; Printing; Protein Array; Puerto Rico; Reader; Reading; Research; Resolution; Screening procedure; Sensitivity and Specificity; Serotyping; Serum; Specificity; Staging; Streptavidin; Syndrome; System; Taiwan; Testing; Texas; Time; Treatment outcome; United States Food and Drug Administration; Vaccines; Viral Antigens; Virus; Virus Diseases; West Nile Encephalitis; West Nile virus; base; biodefense; biomedical scientist; cost; cost effective; cyanine dye 5; design; experience; improved; instrument; man; member; novel; pathogen; point of care; polyclonal antibody; pre-clinical; prototype; secondary infection; viral detection

DESCRIPTION (provided by applicant): Dengue is a mosquito-transmitted acute viral disease of man caused by the Dengue virus, a member of the flaviviridae family. It is endemic in many parts of the world, particularly tropical and sub-tropical regions and quite recently there have been outbreaks in Texas and Hawaii. It has been estimated that there are 100 million new case of Dengue infection per year, up to half a million of which progress to life-threatening Dengue Hemorrhagic Fever. Dengue is classified by NIAID as a re-emerging pathogen and a Category A biodefense agent. Currently there is no vaccine and good management is critical for a successful resolution of the disease. A rapid, accurate diagnosis is the key to clinical decision making. Currently, diagnosis of infection is determined by either IgG or IgM ELISA or PCR. These tests have a number of drawbacks including cost, the time needed to carry them out, the requirement for expensive equipment and their sensitivity and specificity particularly in acute/early stage disease. Hence the need for improved Dengue testing is paramount. InBios International proposes to address this issue by developing a rapid, inexpensive, highly sensitive, point-of-care assay for the detection of viral antigens in the serum of infected individuals. In the pursuit of this objective, we will first identify type-specific Dengue antigens in the sera of patients at different stages of disease by using novel antibody microarrays constructed with a large, unique, panel of anti-dengue Mabs. Once target antigens have been identified we will make lateral flow dipstick assays, or so-called "rapid" tests with the identified monoclonal antibodies and evaluate their performance in several Dengue-endemic regions (Taiwan, Puerto Rico). The sensitivity of the antigen assay will be increased by the use of a specially constructed, high sensitivity hand held fluorescence reader. We intend that the fluorescence reader will be produced at very low cost. In the pursuit of these goals, InBios will draw on its considerable experience in flavivirus research (we have an FDA approved diagnostic for West Nile Virus) and furthermore has put together a world class team of biomedical scientists with peerless expertise in Dengue pathobiology, diagnostic development and prototype instrument design. The aims of this application are to develop a specific antigen test for the early diagnosis of Dengue virus infections. This virus is endemic in many tropical and sub-tropical regions of the world and can be fatal. It is also listed as a bioterrorism agent. Early diagnosis could lead to improved treatment outcomes.

描述（由申请人提供）：登革热是一种由蚊子传播的人类急性病毒性疾病，由黄病毒科成员登革热病毒引起。它在世界许多地方流行，特别是热带和亚热带地区，最近在德克萨斯州和夏威夷爆发了疫情。据估计，每年有 1 亿新感染登革热病例，其中多达 50 万病例发展为危及生命的登革出血热。登革热被 NIAID 归类为重新出现的病原体和 A 类生物防御剂。目前尚无疫苗，良好的管理对于成功解决该疾病至关重要。快速、准确的诊断是临床决策的关键。目前，感染的诊断是通过 IgG 或 IgM ELISA 或 PCR 确定的。这些测试有许多缺点，包括成本、进行测试所需的时间、需要昂贵的设备及其敏感性和特异性，特别是在急性/早期疾病中。因此，改进登革热测试的需求至关重要。 InBios International 建议通过开发一种快速、廉价、高灵敏度的即时检测方法来检测感染个体血清中的病毒抗原来解决这个问题。为了实现这一目标，我们将首先通过使用由大量、独特的抗登革热单克隆抗体构建的新型抗体微阵列来鉴定处于不同疾病阶段的患者血清中的类型特异性登革热抗原。一旦确定了目标抗原，我们将使用已确定的单克隆抗体进行侧流试纸分析或所谓的“快速”测试，并评估其在几个登革热流行地区（台湾、波多黎各）的表现。通过使用特殊构造的高灵敏度手持式荧光读数器，可以提高抗原测定的灵敏度。我们希望荧光阅读器的生产成本非常低。为了实现这些目标，InBios 将利用其在黄病毒研究方面的丰富经验（我们拥有 FDA 批准的西尼罗河病毒诊断方法），此外还组建了一支世界一流的生物医学科学家团队，他们在登革热病理学、诊断开发方面拥有无与伦比的专业知识和原型仪器设计。 该应用的目的是开发一种用于登革热病毒感染早期诊断的特异性抗原测试。这种病毒在世界许多热带和亚热带地区流行，可能致命。它也被列为生物恐怖主义制剂。早期诊断可以改善治疗结果。