Immunoassay for capsular antigen for rapid diagnosis of anthrax

描述（由申请人提供）：抗生素只有在感染的非常早期阶段才能有效对抗炭疽，当时症状是非特异性的，诊断是困难的。因此，早期诊断是治疗新生感染的医学对策的核心。 炭疽杆菌被一个由聚？D-谷氨酸（PGA）。初步研究发现，在肺炭疽动物模型中，PGA会释放到血清和尿液中，PGA的免疫测定是诊断中血培养的有效替代物。PGA出现在血液中的时间或之前，血液样本将产生阳性血培养。然而，与可能需要几天才能产生阳性结果的血液培养不同，快速形式的免疫测定可以在几秒钟到几分钟内产生阳性结果。其他研究发现，EIA可以成功地迁移到侧流免疫色谱（LFI）格式。LFI检测平台具有快速、高灵敏度、易于使用、适应性强和成本效益高的特点。 总的假设是，血液和尿液中PGA的免疫测定是诊断炭疽的血培养的有效替代物。总体目标是将该项目从概念验证转移到LFI形式的免疫测定优化以及使用人样本和家兔和食蟹猴吸入性炭疽模型验证测定。具体目标是：i）生产和优化LFI形式的免疫测定，ii）在实验室环境中评价和验证免疫测定性能，iii）使用动物模型和人类炭疽样本验证免疫测定性能。 这是一个成熟的项目，已经从i）潜在诊断靶点的初始概念发展到ii）研究级免疫测定的开发，iii）动物模型中的概念验证靶点验证，iv）以床旁形式生产原型免疫测定。如果成功，拟议的诊断工具将大大提高应对生物恐怖主义事件的准备程度。

DESCRIPTION (provided by applicant): Antibiotics are effective against anthrax only if given at a very early stage of infection when symptoms are non-specific and diagnosis is difficult. As a consequence, early diagnosis is central to medical countermeasures designed to treat treatment nascent infection. Bacillus anthracis is surrounded by a capsule composed of poly-?-D-glutamic acid (PGA). Preliminary studies found that PGA is shed into serum and urine during animal models of pulmonary anthrax and that immunoassay for PGA is an effective surrogate for the blood culture in diagnosis. PGA appears in blood at or before the time that a blood sample will yield a positive blood culture. However, unlike the blood culture which can take several days to produce positive results, immunoassay in rapid format can produce positive results in seconds to minutes. Additional studies found that the EIA can be successfully migrated to a lateral flow immunochromatographic (LFI) format. The LFI assay platform is rapid, highly sensitive, easy to use, highly adaptable, and cost effective. The overall hypothesis is that immunoassay for PGA in blood and urine is an effective surrogate for the blood culture in diagnosis of anthrax. The overall goal is to move the project from proof-of-concept to optimization of an immunoassay in LFI format and validation of the assay using human samples and models of inhalation anthrax in rabbits and Cynomolgus macaques. The Specific Aims are to i) produce and optimize an immunoassay in LFI format, ii) evaluate and validate immunoassay performance in a laboratory setting and iii) validate immunoassay performance using animal models and samples from human anthrax. This is a mature project that has moved from i) an initial concept for a potential diagnostic target to ii) development a of research-grade immunoassay to iii) proof-of-concept target validation in animal models to iv) production of a prototype immunoassay in point-of-care format. If successful, the proposed diagnostic tool will significantly enhance readiness for a bioterrorism incident.