Invasive aspergillosis (IA) is a deadly fungal infection that occurs in 10% of stem cell transplant patients and 5% of solid organ transplant patients. The National Institutes of Health reports that IA produces more deaths in the United States than any of the other pathogenic fungi. IA is most commonly produced by Aspergillus fumigatus, but other Aspergillus spp. may also produce IA.
The goal of this study is to produce a diagnostic test that will allow for early diagnosis and treatment. Diagnosis of IA is particularly difficult because blood cultures are most often negative; alternatives for diagnosis require histology or culture from sites of infection. Such testing requires use of highly invasive clinical samples that are difficult to obtain from those patients at highest risk for disease.
The approach is to identify proteins that are produced by Aspergillus spp. during infection and are shed into serum or urine. If such proteins can be identified, immunoassays can be constructed that will be rapid, inexpensive and capable of use at the point of patient care. The study uses a novel strategy for target discovery termed In vivo Microbial Antigen Discovery (InMAD).
Results to date have identified proteins that are shed into serum and urine during murine and guinea pig models of IA. Bioinformatics analysis has identified epitopes of these proteins that are unique to Aspergillus spp. that are the most common causes of IA. Production of monoclonal antibodies needed for immunoassay construction is in progress. The ultimate product will be a lateral flow immunoassay or enzyme-linked immunosorbent assay (ELISA) for diagnosis of IA.
Project investigators: Thomas Kozel, Ph.D. (Co-Principal Investigator) and David AuCoin, Ph.D. (Co-Principal Investigator) and Amanda Burnham-Marusich, Ph.D. (Postdoctoral Fellow).
Grant support: This study is supported by NIH grant R21/R33 AI085548, Target discovery and immunoassay for diagnosis of invasive aspergillosis, 2010-2017.