A monoclonal IgM directed against immunodominant catalase B of cell wall of Aspergillus fumigatus exerts anti-A. fumigatus activities

Abstract

Aspergillus fumigatus a ubiquitous fungus has been reported to cause human diseases like allergic pulmonary aspergillosis, aspergilloma, and invasive infection. Invasive aspergillosis is one of the most important causes of mortality in patients with hematological malignancies and in bone marrow transplant recipients. The currently available antifungal drugs mostly target the ergosterol synthesis. However, there are a few antifungals, such as echinocandin and glycolipid papulacandin, with which inhibition of cell wall glucans biosynthesis leads to cessation of growth and cell lysis. Limited spectrum and emergence of resistance has become a serious problem with available antifungals. Therefore, an alternative approach is required for successful treatment of mycoses. In the present study, immunogenic protein profile of A. fumigatus cell wall was generated using 2D-gel electrophoresis and three hybridomas producing monoclonal antibodies (IgM) were selected after fusion experiments. Of these three monoclonal antibodies, MAb-7 exhibited potent in vitro inhibitory activity, which was confirmed by MTT assay, FACS analysis, and immuno-fluorescence studies, and the protein was identified as catalase B using MALDI-TOF-MS.