Antigen Detection Assay for the Diagnosis of Melioidosis

诊断类鼻疽的抗原检测分析

• 批准号: 8490302
• 负责人: David P AuCoin
• 金额: $ 29.97万
• 依托单位: INBIOS INTERNATIONAL, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-15 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8490302
• 关键词: Acute; Address; Affinity; Antibiotic Therapy; Antibiotics; Antibody Affinity; Antigens; Area; Attention; Australia; Bacteria; Bedside Testings; Biological Assay; Blood; Burkholderia pseudomallei; Categories; Centers for Disease Control and Prevention (U.S.); China; Chronic; Classification; Data; Detection; Development; Diagnosis; Diagnostic; Diagnostic Reagent; Diagnostic tests; Disease; Epitopes; Evaluation; Future; Goals; Gold; Gram-Negative Bacteria; Health; Hemagglutination; Hong Kong; Human Resources; Immunoassay; Infection; Laboratories; Lateral; Left; Libraries; Melioidosis; Monitor; Monoclonal Antibodies; Morbidity - disease rate; Patients; Polysaccharides; Preparation; Production; Public Health; Pus; Research; Resistance; Sampling; Schools; Serum; Soil; Southeastern Asia; Symptoms; Taiwan; Thailand; Uncertainty; Universities; Urine; Validation; Work; cost; cost effective; diagnosis standard; effective therapy; experience; improved; in vivo; microorganism antigen; mortality; novel; phase 1 study; phase 2 study; point of care; point-of-care diagnostics; preclinical study; prototype; rapid detection; rapid diagnosis; respiratory; success

DESCRIPTION (provided by applicant): Burkholderia pseudomallei is a Gram-negative bacterium that is the causative agent of melioidosis. The bacterium causes significant morbidity and mortality in tropical regions and endemic areas are expanding. Melioidosis is difficult to trea and diagnose due to the fact that B. pseudomallei is resistant to common antibiotics and symptoms are non-specific. Mortality rates reach 45% and 20% in Thailand and Australia respectively, even with antibiotic treatment. Currently, there is no validated diagnostic product for the diagnosis of melioidosis. Culturing of patient samples is the "gold standard" for diagnosis, however this can take 3-5 days. Our goal is to develop a rapid point-of-care lateral flow immunoassay for the detection of the B. pseudomallei capsular antigen (CPS) directly from patient samples. Our previous studies have determined that the CPS is a shed antigen and a prototype LFI has yielded encouraging results. The goals of the project are to (i) produce a library of high affinity CPS specific mAbs (ii) optimize LFI construction, (iii) determine compatibe sample types and sample preparation and (iv) quantify CPS in patient samples. By completing these goals we hope to produce an optimized LFI that possesses sensitivity equal to or greater than culturing of patient samples. To achieve these goals we have established an experienced team. Dr. AuCoin's laboratory is already collaborating with InBios on development of a prototype LFI. In addition, both groups will work closely with experts in endemic areas (Thailand and Australia) who will be conducting evaluation of the LFI with different sample types.

描述（由申请人提供）：类鼻疽伯克霍尔德氏菌是一种革兰氏阴性细菌，是类鼻疽的病原体。该细菌在热带地区造成显着的发病率和死亡率，并且流行地区正在扩大。由于类鼻疽对常见抗生素具有耐药性且症状非特异性，类鼻疽很难治疗和诊断。即使采用抗生素治疗，泰国和澳大利亚的死亡率也分别达到 45% 和 20%。目前，还没有经过验证的诊断产品可用于诊断类鼻疽。患者样本培养是诊断的“金标准”，但这可能需要 3-5 天。我们的目标是开发一种快速的护理点侧流免疫测定法，用于直接从患者样本中检测类鼻疽杆菌荚膜抗原 (CPS)。我们之前的研究已经确定 CPS 是一种脱落抗原，并且原型 LFI 已取得了令人鼓舞的结果。该项目的目标是 (i) 生成高亲和力 CPS 特异性单克隆抗体库 (ii) 优化 LFI 构建，(iii) 确定兼容的样品类型和样品制备，以及 (iv) 量化患者样品中的 CPS。通过完成这些目标，我们希望产生一种优化的 LFI，其灵敏度等于或大于患者样本培养的灵敏度。为了实现这些目标，我们建立了一支经验丰富的团队。 AuCoin 博士的实验室已经与 InBios 合作开发 LFI 原型。此外，两个小组将与流行地区（泰国和澳大利亚）的专家密切合作，他们将对不同样本类型的 LFI 进行评估。

项目成果

Melioidosis diagnostic workshop, 2013.

• DOI: 10.3201/eid2102.141045
• 发表时间: 2015-02
• 期刊: Emerging infectious diseases
• 影响因子: 11.8
• 作者: Hoffmaster AR;AuCoin D;Baccam P;Baggett HC;Baird R;Bhengsri S;Blaney DD;Brett PJ;Brooks TJ;Brown KA;Chantratita N;Cheng AC;Dance DA;Decuypere S;Defenbaugh D;Gee JE;Houghton R;Jorakate P;Lertmemongkolchai G;Limmathurotsakul D;Merlin TL;Mukhopadhyay C;Norton R;Peacock SJ;Rolim DB;Simpson AJ;Steinmetz I;Stoddard RA;Stokes MM;Sue D;Tuanyok A;Whistler T;Wuthiekanun V;Walke HT
• 通讯作者: Walke HT