We are developing antibody-based reagents for prevention and diagnosis of disease due to Aspergillus. Invasive aspergillosis occurs mainly in severely immunocompromised hosts and our ability to diagnose or treat this disease with antifungal drugs is limited. Therefore, strategies that enhance the host immune response are an attractive area for development. The laboratory is developing monoclonal antibodies (MAbs) that block or delay germination, the transition from the spore form to hyphal growth that is required for A. fumigatus to invade host tissue. Currently, we are focused on one MAb that we made (MAb 318) that inhibits germination in vitro, alters alveolar macrophage-conidia interactions and prolongs survival in experimental murine pulmonary infection. MAb 318 binds to three A. fumigatus proteins. We are distinguishing which interaction inhibits germination. We also are examining mechanisms by which MAb 318 enhances macrophage function and prolongs survival. Long term goals include determining the suitability of MAbs that bind to this target for passive prophylaxis and of the target itself as a vaccine to prevent disease. We also want to understand the role of this protein during germination and identify additional MAbs that prevent germination, as complete inhibition may require binding to more than one target.
