Hybrid ELISA: Simple and specific one-tier assay for Lyme disease
混合 ELISA:针对莱姆病的简单而特异的一层检测
基本信息
- 批准号:10758919
- 负责人:
- 金额:$ 102.5万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-03-06 至 2026-08-31
- 项目状态:未结题
- 来源:
- 关键词:AccountingAlgorithmsAntibiotic ResistanceAntibiotic TherapyAntibioticsAntibodiesAntigensAreaAttentionBacterial AntigensBacterial InfectionsBindingBiological AssayBloodBorreliaBorrelia burgdorferiChronic DiseaseClinicalClinical ResearchCommunicable DiseasesDevelopmentDiagnosisDiagnosticDiagnostic testsDiseaseEnzyme-Linked Immunosorbent AssayEpitopesEuropean UnionEvaluationExanthemaEyeFormulationGeographyGovernmentGrantGrowthHybridsImmunochemistryImmunoglobulin GImmunoglobulin MIndividualInfectionLaboratoriesLegitimacyLocationLyme DiseaseLyme disease diagnosisMarketingMedicalMethodologyMethodsMidwestern United StatesNatureNew EnglandOrder SpirochaetalesPatientsPeptidesPerformancePersonsPhasePhysiciansPredictive ValuePreparationProceduresProcessProteinsProtocols documentationPublic HealthReagentRecombinant ProteinsRecommendationRecording of previous eventsReproducibilityResearch DesignRestRiskRisk FactorsRunningSamplingScreening ResultSensitivity and SpecificitySerologySerology testSerumServicesSiteSpecificityStep TestsSymptomsTest ResultTestingTick-Borne DiseasesTimeTranslationsUnited StatesValidationVector-transmitted infectious diseaseWestern Blottingantibody detectionassay developmentclinical diagnosiscommercial launchcostcross reactivitydiagnostic assayerythema migransin-vitro diagnosticsmanufacturenovelprospectiveprototyperesearch clinical testingscreeningsynthetic peptide
项目摘要
Abstract
Lyme disease, caused by infection with the spirochete Borrelia burgdorferi or closely related species, is the most
common vector-borne disease in the United States, accounting for nearly 500,000 infections per year according
to recent public health estimates. It is also one of the few infectious diseases that requires a two-step laboratory
testing protocol, comprising a screening assay, typically ELISA, followed by a confirmatory immunoblot. This
protocol is followed where the disease has progressed beyond the hallmark erythema migrans rash, or the rash
cannot be identified, and symptoms or history suggest Lyme disease. The two-step protocol is a result of the
poor specificity of most Lyme screening tests, which lead to a high false positive rate. This in turn is due to the
cross-reactive nature of many bacterial antigens, combined with the limitations of conventional ELISA
immunochemistry. In principle, a confirmatory result must be obtained prior to initiating treatment, but in practice,
the multi-day delay that is often incurred in this process frequently leads physicians to prescribe antibiotic
treatment in the absence of definitive lab results. As the vast majority of the more than three million annual Lyme
tests in the U.S. are carried out on individuals who are ultimately found not to have Lyme disease, this practice
leads to the unnecessary prescription and use of antibiotics, contributing to the growth of antibiotic resistance
which has become a significant threat to public health. A first step test with significantly higher specificity would
avoid the need for a second step test and enable clinicians to make informed treatment decisions in a timely
manner, based on credible test results.
This project is aimed at bringing about a significant change in medical practice by reducing Lyme testing from
the current two-step process to a one-step process. To achieve this objective, we have developed a novel ELISA
methodology for Lyme antibody detection that enables exceptionally high assay specificity. The test is based
on well-established, highly specific and sensitive Borrelia antigens in a unique immunochemical format. The
novel ELISA immunochemistry eliminates almost all non-specific reactivity, yielding results comparable in
specificity but higher in sensitivity than those obtained with the conventional two-tier testing protocol.
Consequently, this assay promises to deliver a one-step testing solution for Lyme disease, at a time when
alternatives to the original two-step method are gaining legitimacy at the scientific as well as regulatory level.
In Phase I, we developed a prototype ELISA assay, proving feasibility by demonstrating higher sensitivity and
equivalent specificity on retrospective samples comprising Lyme patients and controls, in comparison with two-
tier testing results. In Phase II, we will complete development of the assay into a commercial product, carry out
prospective and retrospective clinical studies and submit a 510(k) application to FDA for use of the ELISA as a
one-step test for Lyme disease, enabling commercial launch upon approval.
抽象的
莱姆病是由螺旋体伯氏伯氏菌或密切相关的物种引起的,是最多的
美国常见媒介传播疾病,每年占近500,000次感染
根据最近的公共卫生估计。它也是需要两步实验室的少数传染病之一
测试方案,包括筛选测定法,通常为ELISA,然后是确认性免疫印迹。这
遵循该疾病超出标志性红斑偏头疹或皮疹的方案
无法识别,症状或病史表明莱姆病。两步协议是
大多数莱姆筛查测试的特异性较差,这会导致高误报率。反过来,这是由于
许多细菌抗原的交叉反应性,结合常规ELISA的局限性
免疫化学。原则上,必须在开始治疗之前获得确认结果,但实际上
在此过程中经常发生的多天延迟经常导致医生开处方抗生素
在没有确定实验室结果的情况下进行处理。作为超过三百万年莱姆的绝大多数
在美国,对最终发现没有莱姆病的个体进行了这种做法
导致不必要的处方和使用抗生素,导致抗生素耐药性的生长
这已成为对公共卫生的重大威胁。具有更高特异性的第一步测试将
避免进行第二步测试,并使临床医生能够及时做出明智的治疗决定
基于可靠的测试结果的方式。
该项目的目的是通过减少莱姆测试的重大变化。
当前的两步过程到一步过程。为了实现这一目标,我们开发了一种新颖的ELISA
莱姆抗体检测的方法,可实现极高的测定特异性。该测试是基于的
以独特的免疫化学形式建立的良好,高度特异性和敏感的疏褐色抗原。这
新型ELISA免疫化学消除了几乎所有非特异性反应性,得出的结果可比
特异性比使用常规两层测试方案获得的灵敏度更高。
因此,该测定法有望为莱姆病提供一步测试解决方案
原始两步方法的替代方法是在科学和法规水平上获得合法性。
在第一阶段,我们开发了一个原型ELISA分析,通过证明更高灵敏度和
与两种二的相比
层测试结果。在第二阶段,我们将将测定法的开发成商业产品,进行
前瞻性和回顾性临床研究,并向FDA提交510(k)申请,以将ELISA用作
莱姆病的一步测试,在批准后实现商业发布。
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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Andrew E. Levin其他文献
Evaluation of a sequential enzyme immunoassay testing algorithm for Lyme disease demonstrates lack of test independence but high diagnostic specificity.
对莱姆病序贯酶免疫分析测试算法的评估表明缺乏测试独立性,但诊断特异性较高。
- DOI:
- 发表时间:
2018 - 期刊:
- 影响因子:2.9
- 作者:
G. Wormser;Claudia R. Molins;Andrew E. Levin;Susan C. Lipsett;L. Nigrovic;M. Schriefer;J. Branda - 通讯作者:
J. Branda
The Babesia observational antibody (BAOBAB) study: A cross-sectional evaluation of Babesia in two communities in Kilosa district, Tanzania
巴贝虫观察性抗体 (BAOBAB) 研究:坦桑尼亚基洛萨区两个社区巴贝虫横断面评估
- DOI:
10.1371/journal.pntd.0007632 - 发表时间:
2019 - 期刊:
- 影响因子:3.8
- 作者:
E. Bloch;Z. Mrango;M. Kasubi;Jerusha Weaver;Aleksandra Mihailovic;B. Munoz;A. Weimer;Andrew E. Levin;L. Tonnetti;J. Linnen;V. Brès;D. Norris;G. Carpi;S. West - 通讯作者:
S. West
Frequency and magnitude of seroreactivity to <em>Babesia microti</em> in 245 patients diagnosed by PCR in New York State
- DOI:
10.1016/j.diagmicrobio.2020.115008 - 发表时间:
2020-05-01 - 期刊:
- 影响因子:
- 作者:
Susan Madison-Antenucci;Gary P. Wormser;Andrew E. Levin;Susan J. Wong - 通讯作者:
Susan J. Wong
Andrew E. Levin的其他文献
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{{ truncateString('Andrew E. Levin', 18)}}的其他基金
Point-of-care diagnostic test for T. cruzi (Chagas) infection
克氏锥虫(恰加斯)感染的即时诊断测试
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用于诊断癫痫患者神经囊尾蚴病的快速护理点检测
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9909230 - 财政年份:2020
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Rapid Point-of-Care Assay for Diagnosis of Neurocysticercosis in Seizure Patients
用于诊断癫痫患者神经囊尾蚴病的快速护理点检测
- 批准号:
10084274 - 财政年份:2020
- 资助金额:
$ 102.5万 - 项目类别:
Rapid Point-of-Care Assay for Diagnosis of Neurocysticercosis in Seizure Patients
用于诊断癫痫患者神经囊尾蚴病的快速护理点检测
- 批准号:
10699435 - 财政年份:2020
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Hybrid ELISA: Simple and specific one-tier assay for Lyme disease
混合 ELISA:针对莱姆病的简单而特异的一层检测
- 批准号:
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- 批准号:
9978716 - 财政年份:2019
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