Mycology Research Unit: In Vivo Induced Fungal Antigens

真菌学研究单位：体内诱导真菌抗原

• 批准号: 7635201
• 负责人: M. Hong Thi NGUYEN
• 金额: $ 50.19万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-15 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7635201
• 关键词: Mycology; Research; Unit; Vivo; Induced

DESCRIPTION (provided by applicant): The Mycology Research Unit: In Vivo Induced Fungal Antigens Program Project consists of four interrelated research projects and a Clinical Resource Core organized around the identification of C. albicans and A. fumigatus proteins expressed during human infections. The unifying hypothesis of the Program is that selected in vivo induced proteins contribute to the pathogenesis of invasive fungal infections and have potential applications as vaccine, diagnostic and therapeutic targets. The Core, run by Dr. Wingard (University of Florida; UF) will collect sera and tissue samples from patients with C. albicans and A. fumigatus infections. The sera will be used extensively in each of the projects. In Project 1 (Candida antigens involved in site-specific virulence), Dr. Nguyen (UF) will study in vivo induced antigens that she and Dr. Clancy identified by screening a genomic expression library with sera from patients with candidiasis. The contributions of the in vivo induced antigens to pathogenesis will be assessed in models of mucosal and systemic candidiasis. She will also characterize the humoral immune response against recombinant antigens in the serum of patients with candidiasis and controls. In Project 2 (A proteomic approach to host humoral immune response), Dr. Liu (UC-Irvine) will construct C. albicans cell wall protein and blood-induced protein arrays and probe them with sera from patients who survived or died from candidemia. Her goal is to identify immunogenic antigens associated with good prognosis. In Project 3 (Candida in vivo expressed protein as a mannan carrier), Dr. Cutler (TRIC,La) will use cell wall antigens identified in Projects 1 and 2 as carrier proteins in a conjugate mannan vaccine against hematogenous candidiasis. Finally, in Project 4 (Identification of In vivo Induced A. fumigatus Antigens), Dr. Clancy (UF) will adapt the serum-based screening that he and Dr. Nguyen developed to screen A. fumigatus expression libraries. In vivo induced A. fumigatus antigens can then be studied using our investigations of C. albicans antigens as models.

描述（由申请人提供）：真菌学研究单位：体内诱导真菌抗原计划项目包括四个相互关联的研究项目和一个临床资源核心，围绕人类感染期间表达的白色念珠菌和烟曲霉蛋白的鉴定组织。该计划的统一假设是，选定的体内诱导蛋白有助于侵袭性真菌感染的发病机制，并具有作为疫苗、诊断和治疗靶点的潜在应用。由Wingard博士（佛罗里达大学）管理的Core将收集白色念珠菌和烟殖芽胞杆菌感染患者的血清和组织样本。该版本将在每个项目中广泛使用。在项目1（涉及位点特异性毒力的念珠菌抗原）中，Nguyen博士（UF）将研究她和Clancy博士通过筛选念珠菌病患者血清的基因组表达文库确定的体内诱导抗原。体内诱导抗原对发病机制的贡献将在粘膜和全身念珠菌病模型中进行评估。她还将描述念珠菌病患者和对照组血清中针对重组抗原的体液免疫反应。在项目2（宿主体液免疫反应的蛋白质组学方法）中，Liu博士（UC-Irvine）将构建白色念珠菌细胞壁蛋白和血诱导蛋白阵列，并使用念珠菌存活或死亡患者的血清对其进行探测。她的目标是鉴别与预后良好相关的免疫原性抗原。在项目3（假丝酵母体内表达蛋白作为甘露聚糖载体）中，卡特勒博士（TRIC,La）将使用项目1和2中鉴定的细胞壁抗原作为载体蛋白，用于抗血源性念珠菌病的偶联甘露聚糖疫苗。最后，在项目4（体内诱导烟曲霉抗原的鉴定）中，Clancy博士（UF）将采用他和Nguyen博士开发的基于血清的筛选来筛选烟曲霉表达文库。体内诱导的烟曲霉抗原可以用我们对白色念珠菌抗原的研究作为模型来研究。