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

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(申请人提供):目前对莱姆病的检测不是最理想的,因为它需要两个检测平台,包括一个对结果进行主观解释的平台,以及因为它在疾病的早期阶段敏感性较低。莱姆病的病原体伯氏疏螺旋体的感染是通过硬蜱的叮咬传播的,导致病原体负担均匀较低,只有短暂的血液传播阶段,因此直接检测血液等容易接触的组织中的细菌的灵敏度较低。因此,诊断检测依赖于血清学检测来检测针对细菌的抗体。美国疾病控制与预防中心目前建议采用两级检测,初始检测为酶联免疫吸附试验,阳性或可疑结果必须通过免疫印迹确认。在历史上,这两种检测都是用体外培养的细菌的全细胞超声波进行的,尽管现在已知伯氏杆菌螺旋体在从扁虱迁移到哺乳动物宿主时以及在体外培养时会改变它们的蛋白质表达。最近,来自VlsE蛋白的C6多肽的酶联免疫吸附试验已经被开发出来,现在有时被用来代替裂解物的酶联免疫吸附试验。这种仅基于一种抗原的检测结果仍然经常通过免疫印迹来确认,这是耗时的、主观的和昂贵的。我们利用Luminex xMAP技术平台开发了一种新的一步快速多重分析,该平台改进了当前测试的分析平台和所使用的抗原。我们确定了一组抗原,这些抗原由哺乳动物宿主内的螺旋体表达,并对其产生早期的免疫球蛋白G反应。我们开发了一种多重检测方法,它的动态范围比ELISA或免疫印迹法大得多,而且可以更快、更客观地完成。使用多个但具有特异性的抗原也消除了两级检测的需要。我们第一阶段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敏感性,特别是在当前检测失败的情况下。

项目成果

期刊论文数量(0)
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会议论文数量(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
使用蚊子 NeSt1 蛋白预防寨卡病毒感染的疫苗
  • 批准号:
    10194371
  • 财政年份:
    2020
  • 资助金额:
    $ 82.57万
  • 项目类别:
Vaccination against Zika virus infection using mosquito NeSt1 protein
使用蚊子 NeSt1 蛋白预防寨卡病毒感染的疫苗
  • 批准号:
    10081573
  • 财政年份:
    2020
  • 资助金额:
    $ 82.57万
  • 项目类别:
An antigen-detection assay to diagnose Babesia microti infection
诊断田鼠巴贝斯虫感染的抗原检测方法
  • 批准号:
    10403621
  • 财政年份:
    2018
  • 资助金额:
    $ 82.57万
  • 项目类别:
An antigen-detection assay to diagnose Babesia microti infection
诊断田鼠巴贝斯虫感染的抗原检测方法
  • 批准号:
    10082042
  • 财政年份:
    2018
  • 资助金额:
    $ 82.57万
  • 项目类别:
An antigen-detection assay to diagnose Babesia microti infection
诊断田鼠巴贝斯虫感染的抗原检测方法
  • 批准号:
    10200003
  • 财政年份:
    2018
  • 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:
    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
  • 资助金额:
    $ 82.57万
  • 项目类别:
A serologic assay to measure successful Lyme borreliosis antibiotic therapy
测量莱姆疏螺旋体病抗生素治疗是否成功的血清学检测
  • 批准号:
    8715103
  • 财政年份:
    2010
  • 资助金额:
    $ 82.57万
  • 项目类别:

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