Enrichment and validation of urine and serum-specific antigens from acute Lyme disease patient samples
急性莱姆病患者样本中尿液和血清特异性抗原的富集和验证
基本信息
- 批准号:10373787
- 负责人:
- 金额:$ 23.18万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-12-10 至 2023-11-30
- 项目状态:已结题
- 来源:
- 关键词:AcuteAnimalsAntibodiesAntibody ResponseAntigensArthritisBacterial AntigensBiologicalBiological AssayBorrelia burgdorferiCarditisChronicClinicClinicalClinical SensitivityCollaborationsCollectionComplexDataDetectionDevelopmentDiagnosisDiagnosticDiagnostic testsEarly DiagnosisEarly treatmentEnsureEnzyme-Linked Immunosorbent AssayFutureHealthcareHumanImmunoassayImmunoprecipitationImpairmentInfectionInfectious AgentLaboratoriesLyme DiseaseLyme disease diagnosisMacacaMagnetismMass Spectrum AnalysisMethodsModelingNeurologicNevadaOrder SpirochaetalesOutcome StudyPatient AgentsPatient-Focused OutcomesPatientsProceduresProteinsProtocols documentationPublic HealthPublishingRapid diagnosticsRecording of previous eventsResearchSamplingSerologySerology testSerumSourceTechniquesTestingTicksTimeUnited StatesUniversitiesUrineValidationVariantVector-transmitted infectious diseaseWestern Blottingantigen detectionantigen diagnosticbasedesigndetection assayerythema migransexperienceimprovedinnovationmedical schoolsmemberpreventtick-bornetreatment research
项目摘要
ABSTRACT
Lyme borreliosis is the leading vector-borne disease in the United States. Early diagnosis and treatment of
Lyme disease is critical to prevent the development of severe complications such as extensive arthritis, chronic
neurological impairments, and carditis. A critical barrier in the clinic is the inability to diagnose Lyme disease
early during infection in patients that do not develop a distinct erythema migrans. The only FDA cleared tests
for Lyme disease are two-tier serologic assays that are laborious to perform. More importantly, such assays
are unable to diagnose Lyme disease in its early stages due to the time that is required for a patient to develop
an antibody response to the infecting Borrelia burgdorferi (Bb), the causative agent of Lyme disease. In this
proposal, our objective is to identify and validate urine and serum-specific antigens in samples
collected from patients with Lyme disease. Validated antigens will be used, as part of a future proposal, to
develop Bb antigen detection assays for the early diagnosis of Lyme disease. This is a challenging research
endeavor that we believe will require an unwavering focus on the following two hypotheses: First, development
of a diagnostic test detecting only one Bb antigen will not result in a clinically-useful test for early Lyme
disease. We strongly believe that targeting multiple antigens, as opposed to a single antigen, will be required
for the development of a highly-sensitive assay. During our preliminary studies we optimized methods to
discover antigens that are present within samples collected from Lyme patients as well as a tick-borne
macaque model of Lyme disease. Six candidate Bb antigens were identified within serum; these antigens will
be considered for validation in patient samples through this R21 proposal. To demonstrate that the use of the
DIA-MS approach, described in this proposal, will result in the consistent detection of potential antigens results
from a preliminary study in which 5 acute patient serum samples were analyzed using the proposed method.
The analysis found that 243 proteins were detected in all 5 samples, confirming the reliability of the approach.
The reliable detection of Bb-specific antigens from biological samples is a significant diagnostic breakthrough,
however, detection of multiple Lyme antigens will be essential to achieve high clinical sensitivity. Second, a
diagnostic test for early Lyme disease will require patient sample enrichment prior to downstream assays. This
has become clear from our preliminary studies with Lyme samples, as well as our studies to detect other
infectious agents from patient samples. The development of sample enrichment protocols that require minimal
processing will ensure that enrichment is compatible with the workflow of a clinical laboratory. A collaboration
with John Hopkins Lyme Disease Research Center will allow for the inclusion of paired human urine and serum
samples in the discovery and validation stages of the project. Ultimately, simplifying the diagnosis of Lyme
disease will allow for an earlier diagnosis, improved patient outcome, and an easement of Lyme-related
healthcare burdens.
摘要
莱姆病是美国主要的媒介传播疾病。的早期诊断和治疗
莱姆病是至关重要的,以防止严重并发症的发展,如广泛的关节炎,慢性
神经损伤和心脏炎临床上的一个关键障碍是无法诊断莱姆病
在感染早期,患者不会出现明显的游走性红斑。FDA唯一批准的测试
用于莱姆病的两级血清学测定是费力进行的。更重要的是,这种检测
由于患者发展所需的时间,
对莱姆病病原体伯氏疏螺旋体(Bb)的抗体反应。在这
我们的目标是鉴定和验证样本中的尿液和血清特异性抗原
从莱姆病患者身上收集的。作为未来提案的一部分,将使用经验证的抗原,
开发Bb抗原检测方法,用于莱姆病的早期诊断。这是一项具有挑战性的研究
我们认为,这一奋进需要坚定不移地关注以下两个假设:第一,发展
仅检测一种Bb抗原的诊断测试不会导致对早期莱姆病的临床有用的测试
疾病我们坚信,与单一抗原相比,需要靶向多种抗原
用于开发高灵敏度的检测方法。在我们的初步研究中,我们优化了方法,
发现存在于从莱姆病患者以及蜱传病毒收集的样本中的抗原
莱姆病的猕猴模型。在血清中鉴定出六种候选Bb抗原;这些抗原将
考虑通过本R21提案在患者样本中进行验证。为了证明使用
本提案中描述的DIA-MS方法将导致潜在抗原结果的一致性检测
来自初步研究,其中使用所提出的方法分析了5个急性患者血清样品。
分析发现,在所有5个样本中检测到243种蛋白质,证实了该方法的可靠性。
从生物样品中可靠地检测出B b特异性抗原是一项重大的诊断突破,
然而,检测多种莱姆病抗原对于获得高临床灵敏度是必不可少。二是
早期莱姆病的诊断测试将需要在下游测定之前富集患者样品。这
从我们对莱姆病样本的初步研究以及我们对检测其他疾病的研究中,
病人样本中的传染源。开发样品富集方案,
处理将确保富集与临床实验室的工作流程相容。协作
与约翰霍普金斯莱姆病研究中心将允许包括配对的人尿液和血清
在项目的发现和验证阶段,最终,简化莱姆病的诊断
疾病将允许更早的诊断,改善患者的结果,并减轻莱姆相关的
医疗负担。
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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David P AuCoin其他文献
David P AuCoin的其他文献
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{{ truncateString('David P AuCoin', 18)}}的其他基金
Enrichment and validation of urine and serum-specific antigens from acute Lyme disease patient samples
急性莱姆病患者样本中尿液和血清特异性抗原的富集和验证
- 批准号:
10539304 - 财政年份:2021
- 资助金额:
$ 23.18万 - 项目类别:
Point-of-care antigen detection assay for early diagnosis of Ebola virus disease (EVD)
用于早期诊断埃博拉病毒病 (EVD) 的即时抗原检测分析
- 批准号:
9910131 - 财政年份:2020
- 资助金额:
$ 23.18万 - 项目类别:
Identification of Borrelia burgdorferi diagnostic biomarkers in humans and nonhum
人类和非人类伯氏疏螺旋体诊断生物标志物的鉴定
- 批准号:
8783365 - 财政年份:2014
- 资助金额:
$ 23.18万 - 项目类别:
Identification of Borrelia burgdorferi diagnostic biomarkers in humans and nonhum
人类和非人类伯氏疏螺旋体诊断生物标志物的鉴定
- 批准号:
8892078 - 财政年份:2014
- 资助金额:
$ 23.18万 - 项目类别:
Antigen Detection assay for the Diagnosis of Melioidosis
诊断类鼻疽的抗原检测分析
- 批准号:
9084470 - 财政年份:2012
- 资助金额:
$ 23.18万 - 项目类别:
Antigen Detection Assay for the Diagnosis of Melioidosis
诊断类鼻疽的抗原检测分析
- 批准号:
8490302 - 财政年份:2012
- 资助金额:
$ 23.18万 - 项目类别:
Antigen Detection assay for the Diagnosis of Melioidosis
诊断类鼻疽的抗原检测分析
- 批准号:
8883363 - 财政年份:2012
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Antigen Detection Assay for the Diagnosis of Melioidosis
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- 批准号:
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- 资助金额:
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8260262 - 财政年份:2011
- 资助金额:
$ 23.18万 - 项目类别:
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