Antigen Detection assay for the Diagnosis of Melioidosis

性状（由申请方提供）：类鼻疽伯克霍尔德菌是一种革兰氏阴性菌，是类鼻疽病的病原体。这种细菌在热带地区引起显著的发病率和死亡率，流行地区正在扩大。由于B。类鼻疽对普通抗生素有抗药性，症状没有特异性。在泰国和澳大利亚，即使使用抗生素治疗，死亡率也分别达到45%和20%。目前，没有经过验证的诊断产品用于诊断类鼻疽。患者样本的培养是诊断的“金标准”;然而，这可能需要3-7天。我们的目标是开发一种快速的床旁侧流免疫测定（LFI）检测的B。从患者样品中直接提取类鼻疽荚膜抗原（CPS）。I期STTR特定目标侧重于生产抗CPS单克隆抗体（mAb）文库，优化LFI组分和样品制备，并对存档的类鼻疽患者样品进行可行性研究。该II期申请的目的是对包含更高亲和力CPS mAb的原型AMD LFI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的培养。为了实现这些目标，我们组建了一支经验丰富的团队。AuCoin博士的实验室和InBios International之间存在着强大的合作伙伴关系，这导致了令人鼓舞的LFI原型的开发。此外，这两个小组将与流行地区（泰国和澳大利亚）的专家密切合作，他们将使用不同的患者样本类型对LFI进行大型临床前评估。

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.