Antibody isotyping for discrimination of disease stage and diagnosis of early Lyme disease.

用于区分疾病阶段和诊断早期莱姆病的抗体同种型。

• 批准号: 10204992
• 负责人: Maria Gomes-Solecki
• 金额: $ 29.55万
• 依托单位: IMMUNO TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10204992
• 关键词: Acute; Acute Disease; Affinity; Antibodies; Antibody Response; Antigens; Arthritis; Benchmarking; Biological Assay; Biological Markers; Borrelia burgdorferi; Centers for Disease Control and Prevention (U.S.); Clinic; Clinical; Collaborations; Data; Development; Diagnosis; Diagnostic; Diagnostic Specificity; Discrimination; Disease; Early Diagnosis; Enzyme Immunoassay; Evaluation; GTP-Binding Protein alpha Subunits, Gs; Genetic Recombination; Goals; Grant; High Prevalence; Human; IgA1; IgA2; IgE; IgG1; IgG2; IgG3; IgG4; Immune response; Immunodominant Antigens; Immunoglobulin A; Immunoglobulin D; Immunoglobulin G; Immunoglobulin Isotypes; Immunoglobulin M; Immunoglobulins; Infection; Iowa; Laboratories; Laboratory Diagnosis; Lesion; Letters; Licensing; Lyme Arthritis; Lyme Disease; Machine Learning; OspC protein; Patients; Peptidoglycan; Performance; Phase; Proteins; ROC Curve; Recommendation; Reproducibility; Research; Serum; Small Business Innovation Research Grant; Specificity; Techniques; Technology; Testing; Time; Training; Universities; Update; V(D)J Recombination; Visual; Work; antigen binding; base; commercialization; disease diagnosis; erythema migrans; follow-up; improved; lateral flow assay; novel diagnostics; pathogen; tool

ABSTRACT More than 3 million tests are performed each year to support the laboratory diagnosis of human Lyme disease (LD). While the CDC conventional standard two-tier (CSTT) approach for serodiagnosis of LD has worked relatively well when used as recommended, there is plenty of room for improvement. Of a number of weaknesses associated with the supplemental immunoblot of the CSTT the most significant is low reproducibility due to the subjective visual interpretation of results. To overcome these weaknesses the CDC recently updated its recommendations based on a modified STT (MSTT) in that a second EIA can replace the immunoblot. The major goal of this project is to develop an objective, quantitative, multiplex EIA that can detect four antibody isotypes (IgM/D/G/A) and all four IgG subclasses (IgG1/2/3/4) to leverage acquisition of simultaneous antibody profile information on multiple B. burgdorferi antigens to build an assay that can discriminate Lyme disease stage with increased overall sensitivity without incurring in loss of specificity. The novelty of this study relies on: 1) evaluation of B. burgdorferi antigen-specific antibody isotypes and IgG subclasses that can be correlated with Lyme disease stage; and 2) development of new diagnostic tools using machine learning techniques to train and integrate all data and produce an objective result to discriminate early Lyme from early disseminated/late Lyme disease. We expect this Phase I SBIR to allow us to develop a new EIA for serodiagnosis of Lyme disease (isoEIAplex-Ld) and to further an ongoing collaboration with DCN diagnostics for the adaptation of our biomarkers to a new rapid Lateral Flow Assay (see Letter of Support) for a follow up Phase II SBIR .

抽象的 每年进行超过300万个测试以支持人类莱姆的实验室诊断 疾病（LD）。 CDC常规标准两层（CSTT）方法 LD按照建议使用相对较好的效果，有足够的改进空间。 与CSTT的补充免疫印迹相关的许多弱点 由于对结果的主观视觉解释，显着性的可重复性低。克服 这些弱点CDC最近根据修改后的STT（MSTT）更新了建议 因为第二个EIA可以替换免疫印迹。该项目的主要目标是开发 物镜，定量的多重EIA可以检测四种抗体同种型（IgM/d/g/a）和所有四个 IgG子类（IgG1/2/3/4）利用同时获得的抗体概况信息 多个B. burgdorferi抗原，以建立可以区分莱姆病阶段的测定法 提高总体灵敏度而不会导致特异性丧失。这项研究的新颖性依赖于： 1）评估B. burgdorferi抗原特异性抗体同种型和IgG亚类的评估 与莱姆病阶段相关； 2）使用机器开发新的诊断工具 学习技术来培训和整合所有数据并产生客观的结果以及早区分 早期传播/晚期莱姆病的莱姆。我们希望这个阶段我能够让我们发展 莱姆病（Isoiaplex-LD）的新的EIA，用于进一步的合作 使用DCN诊断来适应我们的生物标志物对新的快速横向流量测定法（请参阅 支持信）进行后续第二阶段SBIR。

项目成果

Fatal Multisystem Inflammatory Syndrome in Adult after SARS-CoV-2 Natural Infection and COVID-19 Vaccination.

• DOI: 10.3201/eid2711.211612
• 发表时间: 2021-11
• 期刊: Emerging infectious diseases
• 影响因子: 11.8
• 作者: Grome HN;Threlkeld M;Threlkeld S;Newman C;Martines RB;Reagan-Steiner S;Whitt MA;Gomes-Solecki M;Nair N;Fill MM;Jones TF;Schaffner W;Dunn J
• 通讯作者: Dunn J

A portable immunosensor provides sensitive and rapid detection of Borrelia burgdorferi antigen in spiked blood.

• DOI: 10.1038/s41598-023-34108-9
• 发表时间: 2023-05-09
• 期刊: Scientific reports
• 影响因子: 4.6

A parainfluenza virus 5 (PIV5)-vectored intranasal vaccine for Lyme disease provides long-lasting protection against tick transmitted Borrelia burgdorferi in mice.

副流感病毒 5 (PIV5) 载体鼻内莱姆病疫苗可为小鼠提供针对蜱传播的伯氏疏螺旋体的持久保护。

• DOI: 10.21203/rs.3.rs-3143132/v1
• 发表时间: 2023
• 期刊: Research square
• 作者: Gingerich,MariaCristina;Nair,Nisha;Azevedo,JFilipe;Samanta,Kamalika;Kundu,Suman;He,Biao;Gomes-Solecki,Maria
• 通讯作者: Gomes-Solecki,Maria

Transient Presence of Live Leptospira interrogans in Murine Testes.

• DOI: 10.1128/spectrum.02775-21
• 发表时间: 2022-06-29
• 期刊: MICROBIOLOGY SPECTRUM
• 影响因子: 3.7
• 作者: Shetty, Advait;Kundu, Suman;Vernel-Pauillac, Frederique;Ratet, Gwendoline;Werts, Catherine;Gomes-Solecki, Maria
• 通讯作者: Gomes-Solecki, Maria

Enzyme immunoassays (EIA) for serodiagnosis of human leptospirosis: specific IgG3/IgG1 isotyping may further inform diagnosis of acute disease.

• DOI: 10.1371/journal.pntd.0010241
• 发表时间: 2022-03
• 期刊: PLoS neglected tropical diseases
• 影响因子: 3.8
• 作者: Fortes-Gabriel E;Guedes MS;Shetty A;Gomes CK;Carreira T;Vieira ML;Esteves L;Mota-Vieira L;Gomes-Solecki M
• 通讯作者: Gomes-Solecki M