Informative immunodiagnostics for Lyme disease

莱姆病的信息免疫诊断

• 批准号: 8471641
• 负责人: Alan G. Barbour
• 金额: $ 19.24万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8471641
• 关键词: Acute; Animals; Antibodies; Antigens; Biological Assay; Blinded; Borrelia; Borrelia burgdorferi; Cells; Characteristics; Chronic; Climate; Clinical; Clinical Research; Clinical Trials; Controlled Study; Country; Coupled; Detection; Development; Diagnosis; Disease; Enzyme-Linked Immunosorbent Assay; Etiology; Europe; Evaluation; Future; Genetic Transcription; Goals; Human; Immune response; Immunoassay; Immunoglobulin G; Immunoglobulin M; Immunological Diagnosis; Infection; Label; Laboratories; Lyme Disease; Manufacturer Name; Marketing; Mus; OspC protein; Patients; Pattern; Performance; Phase; Predictive Value; Preparation; Proteins; Proteome; Protocols documentation; Reaction; Recombinant Proteins; Recombinants; Risk; Sampling; Sensitivity and Specificity; Serologic tests; Serum; Social Conditions; Specificity; Staging; Testing; Tick-Borne Diseases; Time; Translations; base; clinical Diagnosis; cost; genome-wide; high risk; improved; meetings; pathogen; research clinical testing; research study; response; screening; tool

DESCRIPTION (provided by applicant): The long-term goal is to provide for an improved immunoassay as an adjunct for the diagnosis of Lyme disease. The assay preferably would have (a) greater sensitivity for detecting infection during early disease, (b) have as a good if no better specificity than currently available assays, alone or in combination, for all stages of disease, and (c) be sufficiently informative that assay interpreters infer the strain of B. burgdorferi a patient is infected with. Specific aims for this R21/R33 application are the following: (1) Use a genome-wide proteome array to interrogate IgM responses of patients with LD and experimental animals infected with B. burgdorferi. The approach will be similar to what was successfully used for studies with an array of IgG responses of humans and mice to this pathogen. The hypothesis that sensitivity of IgM assays is heightened by including two or more OspC type will be tested. (R21 phase) (2) Investigate whether profiles of antibody reactivity to sub-unit antigens provide added-value for inference about the strain of B. burgdorferi someone has been infected with. This will be evaluated in experimental animals infected with different strains and with sera from patients for whom the infecting strain was recovered. Hypotheses that (a) OspC type-specific responses can be distinguished and (b) patterns of reactivity to the BBK07 and BBK12 proteins vary with the infecting strain will be tested. (R21 phase) (3) Develop an immunoassay for eventual clinical testing by (a) selecting the most informative set of recombinant antigens for achieving a high predictive value while minimizing cost, and (b) selecting the most suitable platform, provisionally from among ELISA, immunostrips, and Luminex, for implementation in clinical research evaluation of the assay. The choice of antigens will be from those identified in a previous study, as well as from the results of aims 1 and 2. (R33 phase)

描述（由申请人提供）：长期目标是提供一种改进的免疫测定法，作为诊断莱姆病的辅助手段。该测定优选地具有（a）在早期疾病期间检测感染的更高灵敏度，（B）对于疾病的所有阶段，具有与目前可用的测定（单独或组合）一样好（如果没有更好的话）的特异性，和（c）具有足够的信息，使得测定解释者推断出B的菌株。病人感染的伯氏螺旋体。R21/R33应用的具体目标如下：（1）使用全基因组蛋白质组阵列来询问LD患者和感染B的实验动物的IgM应答。burgdorferi。该方法将类似于成功用于人类和小鼠对该病原体的一系列IgG应答的研究的方法。将检验IgM检测试剂盒灵敏度通过包括两种或更多种OspC类型而提高的假设。(R21阶段）（2）研究抗体对亚单位抗原的反应性谱是否为推断B菌株提供了附加值。有人感染了伯氏螺旋体病。这将在感染不同菌株的实验动物和感染菌株已恢复的患者血清中进行评价。将测试以下假设：（a）可以区分OspC类型特异性应答和（B）对BBK 07和BBK 12蛋白的反应性模式随感染菌株而变化。(R21阶段）（3）通过以下方式开发用于最终临床测试的免疫测定：（a）选择信息量最大的重组抗原集，以实现高预测值，同时最大限度地降低成本，以及（B）暂时从ELISA、免疫试剂条和Luminex中选择最合适的平台，用于在临床研究评估中实施测定。抗原的选择将来自先前研究中确定的抗原以及目标1和2的结果。(R33阶段）

项目成果

Chromosome Sequence of Borrelia miyamotoi, an Uncultivable Tick-Borne Agent of Human Infection.

• DOI: 10.1128/genomea.00713-13
• 发表时间: 2013-09-12
• 期刊: Genome announcements
• 作者: Hue F;Ghalyanchi Langeroudi A;Barbour AG
• 通讯作者: Barbour AG

Borrelia burgdorferi and Borrelia miyamotoi seroprevalence in California blood donors.

• DOI: 10.1371/journal.pone.0243950
• 发表时间: 2020
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Brummitt SI;Kjemtrup AM;Harvey DJ;Petersen JM;Sexton C;Replogle A;Packham AE;Bloch EM;Barbour AG;Krause PJ;Green V;Smith WA
• 通讯作者: Smith WA