Antigen Detection assay for the Diagnosis of Melioidosis

诊断类鼻疽的抗原检测分析

• 批准号: 8780682
• 负责人: David P AuCoin
• 金额: $ 62.11万
• 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 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8780682
• 关键词: Abscess; Acute; Advanced Development; Aerosols; Affinity; Algorithms; Antibiotic Therapy; Antibiotics; Antigens; Archives; Area; Australia; Award; Bacteria; Biological Assay; Biological Markers; Blood typing procedure; Buffers; Burkholderia pseudomallei; Case Study; Centers for Disease Control and Prevention (U.S.); Characteristics; Clinical; Country; Detection; Development; Diagnosis; Diagnostic; Diagnostic Reagent; Diagnostic tests; Disease; Enzyme-Linked Immunosorbent Assay; Feasibility Studies; Genetic Variation; Goals; Gold; Gram-Negative Bacteria; Housing; Human; Immunoassay; In Vitro; Infection; International; Laboratories; Lateral; Lead; Left; Libraries; Melioidosis; Membrane; Modeling; Monoclonal Antibodies; Morbidity - disease rate; Mus; National Institute of Allergy and Infectious Disease; Organ; Patients; Performance; Phase; Polysaccharides; Preparation; Prevalence Study; Production; Public Health; Pus; Reproducibility; Resistance; Sampling; Sepsis; Serum; Site; Skin Tissue; Small Business Technology Transfer Research; Soil; Specificity; Specimen; Sputum; Symptoms; Testing; Thailand; Tropical Disease; Urine; Validation; Variant; Work; cost effective; cross reactivity; design; diagnosis standard; effective therapy; experience; field study; in vivo; mortality; point of care; pre-clinical; preclinical evaluation; prototype; public health relevance; rapid diagnosis; scale up; soft tissue

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 3-7 days. Our goal is to develop a rapid point-of-care lateral flow immunoassay (LFI) for the detection of the B. pseudomallei capsular antigen (CPS) directly from patient samples. Phase I STTR Specific Aims focused on producing a library of anti-CPS monoclonal antibodies (mAbs), optimizing the LFI components and sample preparation, and performing a feasibility study on archived melioidosis patient samples. The objectives of this Phase II application is advanced development and validation of the prototype AMD LFI that incorporates a higher affinity CPS mAb. 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. A strong partnership exists between Dr. AuCoin's laboratory and InBios International that has led to the development of an encouraging prototype LFI. In addition, both groups will work closely with experts in endemic areas (Thailand and Australia) who will be conducting a large preclinical evaluation of the LFI with different patient 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 3-7 天。我们的目标是开发一种快速即时护理侧流免疫测定 (LFI)，用于直接从患者样本中检测假鼻疽伯克氏菌荚膜抗原 (CPS)。第一阶段 STTR 的具体目标侧重于生成抗 CPS 单克隆抗体 (mAb) 库、优化 LFI 成分和样品制备，并对存档的类鼻疽患者样品进行可行性研究。该 II 期应用的目标是对包含更高亲和力 CPS mAb 的 AMD LFI 原型进行高级开发和验证。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 博士的实验室与 InBios International 之间建立了牢固的合作伙伴关系，从而开发出了令人鼓舞的 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，他们将对不同患者样本类型的 LFI 进行大型临床前评估。