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临床资源核心组成，该中心围绕识别在人类感染过程中表达的白色念珠菌和烟曲霉菌蛋白而组织。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。核心中心由Wingard博士(佛罗里达大学；UF)运营，将收集白色念珠菌和烟曲霉菌感染患者的血清和组织样本。血清将在每个项目中广泛使用。在项目1(念珠菌抗原参与特定部位的毒力)中，Nguyen博士(UF)将在体内研究她和Clancy博士通过筛选来自念珠菌病患者血清的基因组表达文库来鉴定的诱导抗原。体内诱导的抗原对发病机制的贡献将在黏膜和系统性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(一种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，并用存活或死于念珠菌症的患者的血清进行检测。她的目标是确定与良好预后相关的免疫原性抗原。在项目3(假丝酵母菌体内表达的蛋白质作为甘露聚糖载体)中，Cutler博士将使用项目1和2中确定的细胞壁抗原作为结合甘露聚糖疫苗的载体蛋白来对抗血源性念珠菌病。最后，在项目4(体内诱导烟曲霉菌抗原的鉴定)中，Clancy博士(UF)将采用他和Nguyen博士开发的基于血清的筛选方法来筛选烟曲霉菌表达文库。以我们对白色念珠菌抗原的研究为模型，可以研究体内诱导的烟曲霉菌抗原。

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.