Mycology Research Unit: In Vivo Induced Fungal Antigens

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围绕C. albicans和A.在人类感染期间表达的烟曲霉蛋白。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; UF）运行的核心将从C. albicans和A.烟曲霉感染在每个项目中将广泛使用sera。在项目1（涉及位点特异性毒力的念珠菌抗原）中，Nguyen博士（UF）将研究体内诱导抗原，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来鉴定这些抗原。将在粘膜和系统性念珠菌病模型中评估体内诱导抗原对发病机制的贡献。她还将描述念珠菌病患者和对照血清中重组抗原的体液免疫应答。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C。白色念珠菌细胞壁蛋白和血液诱导蛋白阵列，并用来自存活或死于念珠菌血症的患者的血清对其进行探测。她的目标是鉴定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甘露聚糖结合疫苗的载体蛋白。最后，在项目4（体内诱导的A. Clancy博士（UF）将采用他和Nguyen博士开发的基于血清的筛查方法来筛查A。烟曲霉表达文库。体内诱导A.然后可以使用我们对烟曲霉的研究来研究烟曲霉抗原。白念珠菌抗原作为模型。

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.