Diagnostic Assays for early Lyme Borreliosis using in-vivo expressed antigens
使用体内表达抗原诊断早期莱姆疏螺旋体病
基本信息
- 批准号:8876556
- 负责人:
- 金额:$ 82.57万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-07-01 至 2018-06-30
- 项目状态:已结题
- 来源:
- 关键词:AntibioticsAntibodiesAntibody ResponseAntigensBacteriaBacterial AntigensBindingBiological AssayBiteBlack-legged TickBloodBody FluidsBorrelia burgdorferiCase StudyCellsCenters for Disease Control and Prevention (U.S.)ClinicalDetectionDiagnosisDiagnosticDiagnostic testsDiseaseEarly DiagnosisEnzyme-Linked Immunosorbent AssayEpitopesHealthImmunoblottingImmunoglobulin GImmunoglobulin MIn VitroInfectionLyme DiseaseMeasurableMedicalMethodsMolecular WeightMovementOne-Step dentin bonding systemOrder SpirochaetalesPatientsPatternPeptidesPerformancePhasePhysiciansPlagueProteinsPublic HealthReadingReportingSamplingSensitivity and SpecificitySerologic testsSerologicalSerumSkinSpecificityStagingStep TestsSymptomsSyndromeTechnologyTestingTicksTimeTissuesUnited StatesVector-transmitted infectious diseaseWorkaccurate diagnosisbasecross reactivitydiagnostic assaydisease diagnosiserythema migransimprovedin vivopathogenphase 1 studyprotein expressionresearch studyresponse
项目摘要
DESCRIPTION (provided by applicant): Current testing for Lyme disease is suboptimal because it requires two assay platforms, including one with subjective interpretation of results, and because it has lower sensitivity in the early stage of the illness. Infection with Borrelia burgdorferi, the causative agent of Lyme disease, is transmitted by the bite of an Ixodid tick and results in uniformly low pathogen burdens with only a transient bloodborne phase, so that the sensitivity of direct detection assays of the bacteria in easily accessible tissues such as the blood is low. Diagnostic testing therefore relies on serologic assays to detect antibodies to the bacteria. The CDC currently recommends a two-tier assay with an initial ELISA, and positive or equivocal results must be confirmed by immunoblot. Historically both assays were performed with whole cell sonicate of in vitro cultured bacteria even though it is now known that B. burgdorferi spirochetes alter their protein expression when they move from the tick to the mammalian host and when they are cultured in vitro. More recently an ELISA for the C6 peptide from the VlsE protein has been developed and is now sometimes used instead of the lysate ELISA. The results of this assay, which is based on just one antigen, are still often confirmed by immunoblot that is time consuming, subjective, and expensive. We have developed a new one-step rapid multiplex assay using the Luminex xMAP Technology platform that improves upon both the assay platform of the current tests and the antigens used. We identified a panel of antigens that are expressed by spirochetes within the mammalian host and to which early IgG responses are generated. We have developed a multiplex assay that has a much larger dynamic range than ELISA or immunoblot, and can be completed more rapidly and objectively. The use of multiple but specific antigens also obviates the need for two-tier testing. Preliminary results from our Phase I study also suggest that our assay has improved sensitivity for detecting early infections, particularly when the current assays fail.
描述(由申请人提供):目前的莱姆病检测是次优的,因为它需要两个检测平台,包括一个主观解释的结果,因为它在疾病的早期阶段具有较低的灵敏度。莱姆病的病原体伯氏疏螺旋体(Borrelia burgdorferi)的感染通过硬蜱(Ixodid tick)的叮咬传播,并且导致均匀低的病原体负荷,仅具有短暂的血液传播阶段,使得在容易接近的组织(例如血液)中细菌的直接检测测定的灵敏度低。因此,诊断测试依赖于血清学测定来检测细菌的抗体。CDC目前建议使用初始ELISA的双层测定法,阳性或可疑结果必须通过免疫印迹法确认。历史上,这两种测定都是用体外培养细菌的全细胞超声处理物进行的,尽管现在已知B。当伯氏螺旋体从蜱转移到哺乳动物宿主时以及当它们在体外培养时,它们改变了它们的蛋白质表达。最近,已经开发了用于来自VlsE蛋白的C6肽的ELISA,并且现在有时使用该ELISA代替裂解物ELISA。这种检测方法仅基于一种抗原,其结果仍然经常通过耗时、主观和昂贵的免疫印迹来确认。我们使用Luminex xMAP技术平台开发了一种新的一步快速多重检测方法,该方法改进了当前检测的检测平台和所用抗原。我们鉴定了一组由哺乳动物宿主内的螺旋体表达的抗原,并对其产生早期IgG应答。我们开发了一种多重检测方法,其动态范围比ELISA或免疫印迹法大得多,并且可以更快速、更客观地完成。使用多种但特异性的抗原也避免了两级测试的需要。我们的I期研究的初步结果也表明,我们的检测方法提高了检测早期感染的灵敏度,特别是当目前的检测方法失败时。
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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Michel Ledizet其他文献
Michel Ledizet的其他文献
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{{ truncateString('Michel Ledizet', 18)}}的其他基金
Vaccination against Zika virus infection using mosquito NeSt1 protein
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Vaccination against Zika virus infection using mosquito NeSt1 protein
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An antigen-detection assay to diagnose Babesia microti infection
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10082042 - 财政年份:2018
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An antigen-detection assay to diagnose Babesia microti infection
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- 批准号:
10200003 - 财政年份:2018
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$ 82.57万 - 项目类别:
A Lyme disease vaccine using newly identified in-vivo expressed antigens
使用新鉴定的体内表达抗原的莱姆病疫苗
- 批准号:
8455815 - 财政年份:2013
- 资助金额:
$ 82.57万 - 项目类别:
A Lyme disease vaccine using newly identified in-vivo expressed antigens
使用新鉴定的体内表达抗原的莱姆病疫苗
- 批准号:
8601286 - 财政年份:2013
- 资助金额:
$ 82.57万 - 项目类别:
Diagnostic Assays for early Lyme Borreliosis using in-vivo expressed antigens
使用体内表达抗原诊断早期莱姆疏螺旋体病
- 批准号:
8782201 - 财政年份:2012
- 资助金额:
$ 82.57万 - 项目类别:
Diagnostic Assays for early Lyme Borreliosis using in-vivo expressed antigens
使用体内表达抗原诊断早期莱姆疏螺旋体病
- 批准号:
8315248 - 财政年份:2012
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$ 82.57万 - 项目类别:
A serologic assay to measure successful Lyme borreliosis antibiotic therapy
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8715103 - 财政年份:2010
- 资助金额:
$ 82.57万 - 项目类别:
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