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Flaviviridae家族成员登革热病毒引起的蚊子传播的急性病毒病。它在世界许多地方，尤其是热带和亚热带地区，这是地方性的，最近在德克萨斯州和夏威夷发生了爆发。据估计，每年有1亿例新的登革热感染病例，其中一百万次危及生命的登革热大量发烧。登革热被NIAID归类为重新出现的病原体，而生物探测剂类别则被分类。目前没有疫苗，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。当前，感染的诊断由IgG或IgM ELISA或PCR确定。这些测试具有许多缺点，包括成本，执行它们所需的时间，对昂贵的设备的要求以及其敏感性和特异性，尤其是在急性/早期疾病中。因此，需要改进的登革热测试至关重要。 INBIOS International建议通过开发快速，廉价，高度敏感的护理测定法，以检测感染个体的血清中病毒抗原。为了追求这一目标，我们将首先使用具有大型，独特的抗登记剂MAB的大型抗体微阵列，在疾病不同阶段的患者血清中识别患者血清中的特异性登革热抗原。一旦确定了靶抗原，我们将对已鉴定的单克隆抗体进行侧向流动量测定，或所谓的“快速”测试，并评估其在几个登革热 - 流行区域（台湾，波多黎各）中的性能。通过使用专门构建的高灵敏度手持荧光读取器，将提高抗原测定法的灵敏度。我们打算以非常低的成本生产荧光读取器。为了实现这些目标，INBIOS将借鉴其在Flavivirus研究中的丰富经验（我们拥有FDA批准的西尼罗河病毒诊断诊断），此外，将拥有无与伦比的专业知识的世界一流的生物医学科学家团队组成了Dengengue病理病理学，诊断和原型仪器设计。 该应用的目的是为早期诊断登革热病毒感染而开发特定的抗原测试。在世界上许多热带和亚热带地区，这种病毒是地方性的，可能是致命的。它也被列为生物恐怖剂。早期诊断可能会改善治疗结果。