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）：Burkholderia pseudomallei是一种革兰氏阴性细菌，是Melioidosis的病因。细菌在热带地区和流行地区引起明显的发病率和死亡率正在扩大。由于假单胞菌对常见抗生素具有抗性，并且症状是非特异性的，因此很难进行梅尔塞多利份病。即使接受抗生素治疗，泰国和澳大利亚的死亡率分别达到45％和20％。当前，尚无诊断诊断梅利前病的诊断产品。培养患者样品是诊断的“黄金标准”，但这可能需要3-5天。我们的目标是直接从患者样品中直接从患者样品中检测出快速的护理侧向流免疫测定。我们以前的研究确定CPS是一种抗原，原型LFI产生了令人鼓舞的结果。该项目的目标是（i）产生一个高亲和力CPS特异性mAB的库（ii）优化LFI结构，（iii）确定兼容样品样品类型和样品制备，并且（iv）在患者样品中量化CPS。通过完成这些目标，我们希望产生优化的LFI，其具有等于或更大的患者样品的灵敏度。为了实现这些目标，我们建立了一个经验丰富的团队。 Aucoin博士的实验室已经与INBIO合作，开发了原型LFI。此外，这两个小组将与流行地区（泰国和澳大利亚）的专家紧密合作，他们将对具有不同样本类型的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