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: 6818972
• 负责人: M. Hong Thi NGUYEN
• 金额: $ 75.34万
• 依托单位: UNIVERSITY OF FLORIDA
• 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/6818972
• 关键词: Aspergillus; Candida albicans; clinical research; fungal antigens; human tissue; laboratory mouse; mycosis

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由四个相互关联的研究项目和一个临床资源核心组成，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而组织。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。该核心由 Wingard 博士（佛罗里达大学；佛罗里达大学）负责，将从白色念珠菌和烟曲霉感染患者身上收集血清和组织样本。该血清将在每个项目中广泛使用。在项目 1（参与位点特异性毒力的念珠菌抗原）中，Nguyen 博士（UF）将研究她和 Clancy 博士通过用念珠菌病患者血清筛选基因组表达文库而鉴定的体内诱导抗原。将在粘膜和全身念珠菌病模型中评估体内诱导抗原对发病机制的贡献。她还将表征念珠菌病患者和对照者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，刘博士（加州大学欧文分校）将构建白色念珠菌细胞壁蛋白和血液诱导蛋白阵列，并用念珠菌血症幸存或死亡患者的血清对其进行探测。她的目标是识别与良好预后相关的免疫原性抗原。在项目 3（念珠菌体内表达蛋白质作为甘露聚糖载体）中，Cutler 博士（TRIC，La）将使用项目 1 和 2 中鉴定的细胞壁抗原作为抗血源性念珠菌病的结合甘露聚糖疫苗中的载体蛋白质。最后，在项目 4（体内诱导烟曲霉抗原的鉴定）中，Clancy 博士（佛罗里达大学）将采用他和 Nguyen 博士开发的基于血清的筛选方法来筛选烟曲霉表达文库。然后可以使用我们对白色念珠菌抗原的研究作为模型来研究体内诱导的烟曲霉抗原。