Develop of Diagnostic Reagents for Detection of Francisella & Francisella Infecti
弗朗西斯氏菌检测诊断试剂的研制
基本信息
- 批准号:7649088
- 负责人:
- 金额:$ 34.04万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2008
- 资助国家:美国
- 起止时间:2008-03-01 至 2009-02-28
- 项目状态:已结题
- 来源:
- 关键词:AffinityAntibodiesAntigensBacteriaBacteriophage M13BacteriophagesBindingBiologicalBiological AssayBuffersCategoriesCellsChimera organismClinicalCommunicable DiseasesComplexDetectionDevelopmentDiagnosticDiagnostic ReagentElementsEnvironmentEnzyme-Linked Immunosorbent AssayEpitopesFacility Construction Funding CategoryFrancisellaFrancisella tularensisGoalsHumanImmune responseImmunodominant AntigensImmunoglobulin FragmentsImmunoglobulinsInfectionInfectious AgentInstitutesLeadLibrariesLigand BindingMembrane ProteinsMolecularMutagenesisOpen Reading FramesOrganismPersonsPhage DisplayPolymerase Chain ReactionProteinsPublic HealthRangeReagentReportingResearchSamplingScheduleScienceSerumSignal TransductionSurfaceSurface Plasmon ResonanceSystemTadpolesTailTechnologyTimeTularemiaValidationWestern Blottingassay developmentbasebiodefensedesign and constructionimprovedin vivopathogensensortoolvector
项目摘要
Francisella tularensis, the causative agent of tularemia, is one of the most infectious bacteria known and is a
Category A biodefense concern. Diagnostic tools that detect Francisella and other select agents are among
the critical needs identified by the NIH/NIAID that are targeted for immediate development and are the focus
of this proposal. Two key components of a successful diagnostic are a high-affinity sensor domain that binds
directly to the targeted organism, or to a product secreted by the organism, and a signal domain that
indicates when the sensor has bound the target molecule. We are using proven technologies: single-chain
variable domain antibody fragment- (scFv-) phage-display, tadpole protein-DNA chimeras, real-time PCR
and the results from our antigen discovery research to create powerful diagnostics that will detect the
presence of Francisella tularensis (Ft) in biological and environmental samples as well as immune responses
directed against Ft.
In this report, we show that a specific tadpole that recognizes mammalian immunoglobulin can be used with
a complex biological sample (serum) to detect an immune response mounted against Ft. In initial assays, a
Ft-specific immune response is detected in serum that is diluted up to 10,000-fold. This report also includes
progress in using phage-display scFv antibody libraries for the development of sensors for Ft-specific
targets. In other systems these reagents have been shown to be up to a million-fold more sensitive than
what is possible using enzyme-linked immunosorbent assays (ELISA). Furthermore, these diagnostics will
be able to identify target molecules over a wide dynamic range of concentrations. This strategy can be
applied to the development of diagnostic reagents that recognize any given target and could lead to a
pipeline that generates sensitive diagnostic tools for many biodefense/infectious disease pathogens.
The bacterium that causes tularemia is one of the most infectious agents known and is a serious biodefense
threat. Greatly needed are tools that can detect minute quantities of the organism and/or that can detect
whether a person has been infected by the organism early in the course of infection. We are using cutting
edge strategies to create molecules that can identify tiny amounts of the organism and that provide a
sensitive readout as to the presence or absence of the organism using a common assay. The strategies
used to create this powerful tool can easily be adapted to create similar reagents for any biodefense or
infectious disease concern.
土拉热弗朗西斯菌是土拉菌病的病原体,是已知最具传染性的细菌之一,也是一种
A类生物防御问题检测弗朗西斯菌和其他选择性病原体的诊断工具包括
NIH/NIAID确定的关键需求,这些需求是针对立即发展的,是重点
这一提议。成功诊断的两个关键组成部分是一个高亲和力的传感器域,
直接与靶生物或生物分泌的产物结合的信号结构域,和
指示传感器何时结合目标分子。我们使用成熟的技术:单链
可变区抗体片段-噬菌体展示,蝌蚪蛋白-DNA嵌合体,实时荧光PCR
以及我们的抗原发现研究的结果,以创建强大的诊断方法,
生物和环境样品中土拉热弗朗西丝菌(Ft)的存在以及免疫反应
针对FT。
在这份报告中,我们表明,一个特定的蝌蚪,认识到哺乳动物免疫球蛋白,可用于与
复杂的生物样品(血清),以检测针对Ft的免疫应答。在初始测定中,
在稀释至10,000倍的血清中检测到FT特异性免疫应答。本报告还包括
利用噬菌体展示单链抗体库开发抗Ft特异性抗体传感器的进展
目标的在其他系统中,这些试剂已被证明比传统的试剂灵敏高达百万倍。
酶联免疫吸附试验(ELISA)。此外,这些诊断将
能够在较宽的动态浓度范围内识别目标分子。该策略可
应用于诊断试剂的开发,识别任何给定的目标,并可能导致
这条管道为许多生物防御/传染病病原体提供了敏感的诊断工具。
引起兔热病的细菌是已知的最具传染性的病原体之一,是一种严重的生物防御
威胁非常需要的是可以检测微量生物体和/或可以检测
一个人是否在感染过程的早期被该生物体感染。我们用切割
边缘策略,以创造分子,可以识别微量的有机体,并提供一个
使用普通测定法,灵敏地读出是否存在生物体。的战略
用于创建这个强大的工具可以很容易地适应任何生物防御或
传染病的关注。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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GEORGE M WEINSTOCK其他文献
GEORGE M WEINSTOCK的其他文献
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{{ truncateString('GEORGE M WEINSTOCK', 18)}}的其他基金
Genomic Comparison of Infectious Strains E. Faecalis
传染性粪肠球菌菌株的基因组比较
- 批准号:
7032244 - 财政年份:2005
- 资助金额:
$ 34.04万 - 项目类别:
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