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）：长期目标是提供改进的免疫测定作为莱姆病诊断的辅助手段。该测定优选地(a)对于检测早期疾病期间的感染具有更高的灵敏度，(b)对于疾病的所有阶段，单独或组合地具有与目前可用的测定一样好的特异性(如果没有更好的话)，并且(c)足够检测解释员推断患者感染的伯氏疏螺旋体菌株的信息。 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检测 LD 患者和感染伯氏疏螺旋体的实验动物的 IgM 反应。该方法将类似于人类和小鼠对该病原体的一系列 IgG 反应的成功研究。将测试通过包含两种或多种 OspC 类型来提高 IgM 检测灵敏度的假设。 （R21 阶段） (2) 研究抗体对亚单位抗原的反应性特征是否为推断某人感染的伯氏疏螺旋体菌株提供附加价值。这将在感染不同菌株的实验动物和恢复感染菌株的患者血清中进行评估。将测试以下假设：(a) OspC 类型特异性反应可以区分，(b) BBK07 和 BBK12 蛋白的反应模式随感染菌株而变化。 （R21 阶段）（3）开发用于最终临床测试的免疫测定法，方法是（a）选择信息最丰富的重组抗原集，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 中选择最合适的平台、免疫试纸条和 Luminex，用于在临床研究评估中实施该检测。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

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

Unique Strain of Borrelia miyamotoi in Ixodes pacificus Ticks, California, USA.

• DOI: 10.3201/eid2212.152046
• 发表时间: 2016-12
• 期刊: Emerging infectious diseases
• 影响因子: 11.8
• 作者: Cook VJ;Fedorova N;Macdonald WP;Lane RS;Barbour AG
• 通讯作者: Barbour AG

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