FUNGAL ANTIGENS AND ANTIFUNGAL RESPONSE

点击翻译按钮获取中文摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The common mold, Aspergillus fumigatus, is an opportunistic pathogen and the most frequently isolated causative agent of invasive aspergillosis. The disease is often contracted by immunocompromised hosts, including cancer patients, with reported mortality rates > 80%. Our long-term goals are to develop a vaccine and to provide better means for the early diagnosis and monitoring of aspergillosis. Our specific hypotheses are: 1) certain aspergillus antigens have an immunoprotective effect, and 2) some antigens may serve as indicators of early stages of aspergillus infections. We base our hypotheses on the following observations. First, mice vaccinated with crude fungal protein extracts or viable conidia survive infection following immunosuppression (e.g., with corticosteroid treatment). Second, the fungus actively secretes a variety of specific proteins and peptides at different stages of its lifecycle. More than 60 antigens and allergens of Aspergillus have been described (1-4). However, only one of them, the polysaccharide galactomannan, is routinely assayed to diagnose Aspergillus infections. Based on these observations, our experimental focus is on the identification and structural and immunological characterization of A. fumigatus antigens. We plan to utilize and improve novel mass spectrometric techniques to detect and identify proteins and peptides of fungal origin from complex mixtures such as culture supernatants, bronchoalveolar lavage (BAL) fluid, blood and urine.