Recent advances in i) treatment of cancer patients, ii) hematopoietic stem cell and organ transplantation, iii) use
of potent immunosuppressive drugs and iv) advanced medical care have created an expanding population of
patients at high risk for invasive fungal diseases (IFD) produced by common environmental molds (aspergillosis,
mucormycosis and fusariosis) and normally commensal yeast (candidiasis). Numerous studies have shown that
early diagnosis and treatment with the right antifungal agent will improve patient outcome.
The goal of this translational research project is a multiplexed immunoassay that will use serum/plasma or urine
as a clinical specimen for diagnosis of early-stage infection by Aspergillus spp., Fusarium spp., the Mucorales,
and Candida spp. The target patient population will be individuals who are at high risk for fungal infection due to
use of immunosuppressive drugs or advanced medical care. The approach will be an immunoassay that detects
cell wall mannans of each fungus that are shed into body fluids during infection. The product will be an
immunoassay, most likely in the lateral flow immunoassay (LFIA) format, for use at primary health-care settings.
The immunoassay will be sensitive, specific, rapid, inexpensive, and user friendly.
There are four Specific Aims. Aim 1 will further develop and validate high-quality monoclonal antibodies (mAbs)
specific for mannan epitopes that are unique to each of the targeted groups of fungi. Aim 2 will determine the
analytical sensitivity of an immunoassay that would be needed to detect early-stage infection using specimens
from humans and murine models. Aim 3 will develop multiplexed immunoassays that have the analytical
sensitivity needed for early diagnosis. Aim 4 will assess clinical performance of prototype immunoassays using
plasma and urine from animal models and patients with IFD.
This study addresses a critical unmet need for diagnosis of increasingly common and fatal opportunistic fungal
infections that occur in high risk patients. If successful, the multiplexed assay will be a game changer for patient
care. The proposal is supported by a strong premise from the literature and solid preliminary results. These
preliminary studies, coupled with the existing paradigm for using immunoassays that target shed cell wall
mannans for diagnosis of IFD, make the probability for success very high.