Point-of-care immunoassay for diagnosis of histoplasmosis in HIV/AIDS

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 1R41AI096945-01
Agency Tracking Number: R41AI096945
Amount: $588,749.00
Phase: Phase I
Program: STTR
Awards Year: 2011
Solicitation Year: 2011
Solicitation Topic Code: NIAID
Solicitation Number: PA10-051
Small Business Information
DUNS: 099550915
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 (405) 360-4669
Business Contact
Phone: (405) 360-4669
Email: sean-bauman@immy.com
Research Institution
 Office of Sponsored Projects
204 Ross Hall Mailstop 325
RENO, NV, 89557-
 () -
 Nonprofit college or university
DESCRIPTION (provided by applicant): Progressive disseminated histoplasmosis is a common and life-threatening fungal infection among patients with HIV/AIDS in the United States and Latin America. Incidence rates in HIV/AIDS can be gt20%, with mortality rates gt30% in resource-limited countries where the fungus, Histoplasma capsulatum, is endemic. Early diagnosis and treatment are essential to reducing this high mortality rate. Diagnosis currently depends on culture or histopathology. These methods have lowsensitivity, are time consuming, are expensive, and require trained personnel. An alternative approach is an immunoassay to detect H. capsulatum polysaccharide in serum or urine. The target antigen is believed to be a cell wall galactomannan. Studies to date have found a high sensitivity for such assays. However, immunoassay for Histoplasma antigen i) is currently available only in ELISA format through use of a reference laboratory, ii) is not commercially available for distribution in resource-limited countries, iii) is dependent on the use of polyclonal rabbit antibodies (pAbs), and iv) is not amenable to point-of-care (POC) use. Our overall hypothesis is that an immunoassay for POC diagnosis of disseminated histoplasmosis in HIV/AIDS can be constructed with high-affinity monoclonal antibodies (mAbs) that target the polysaccharide antigen of H. capsulatum that is shed into serum and urine during infection. A corollary to this hypothesis is that the use of appropriate pairs of mAbs for assay construction will enable targeting of common and unique H. capsulatum epitopes, providing a control over assay specificity that is not possible with pAbs. The first Specific Aim is to produce polysaccharide antigens suitable for screening of hybridomas and evaluation ofmAb specificity. The second Specific Aim is to produce a library of mAbs reactive with the spectrum of epitopes found on the Histoplasma polysaccharide antigen that is shed into serum and urine. If the goals of this Phase I are achieved, Phase II will usemAbs from Phase I to construct and evaluate an immunoassay in POC format. Our preferred assay platform would be the lateral flow immunochromatographic (dipstick) assay. If successful, this translational research project could dramatically decrease mortality from histoplasmosis through earlier diagnosis and treatment. Importantly, this can be done at the low cost needed in resource-limited countries. PUBLIC HEALTH RELEVANCE: Progressive disseminated histoplasmosis is a common and life-threatening, opportunistic fungal infection among patients with HIV/AIDS in the United States and Latin America. This is a translational research study whose goal is an immunoassay in point-of-care format for rapid diagnosis of histoplasmosis in resource-limited countries. If successful, the project could dramatically reduce mortality in endemic regions through early diagnosis and treatment.

* Information listed above is at the time of submission. *

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