Immunoassay for capsular antigen for rapid diagnosis of anthrax

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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.