CORE--ANIMAL

尽管动物模型有先天的局限性，但小鼠模型是人类念珠菌病的良好近似模型。在人类和小鼠中，肾脏是播散性念珠菌病发病过程中的靶器官，真菌可以迁移到两种类型哺乳动物的中枢神经系统。阴道和肠粘膜感染可以在小鼠中建立，这些部位的耐热机制可能与人类相似。巨噬细胞和嗜中性粒细胞的相互作用和这些细胞类型的杀念珠菌活性在小鼠和人分离的细胞中处于相似的水平。小鼠也可以用作预测抗念珠菌药物在人体中的疗效的起点。这些优点沿着许多种类的近交系和远交系小鼠、各种相关基因敲除小鼠的选择，以及化学和免疫试剂的可用库，使得念珠菌病的小鼠模型对于鉴定待用于疫苗方案的候选抗原非常重要。小鼠和家兔将用作开发物，以开发针对MRU的Cutler、Edwards和Mitchell项目的各种疫苗候选抗原的多克隆抗体。小鼠多克隆抗血清将用于被动转移实验，以确定针对特定抗原制备物的抗体是否赋予未处理小鼠对念珠菌病的抗性。我们在这方面有着丰富的经验。将使用家兔制备大量抗候选抗原的抗血清，用于亲和纯化、酵母细胞上或酵母细胞中特异性抗原的定位、功能阻断实验和其他适当应用。动物中心为所有四个项目提供支持服务。具体而言，核心将：i.）。 协助每个项目负责人开发、设计和评估实验，以确定疫苗制剂和抗体对正常和贫血小鼠实验性念珠菌病的体内效力。ii）培养小鼠和兔抗各种念珠菌疫苗候选抗原和模拟这些抗原的肽的多克隆抗体，如[由每个项目负责人提供]。（三）整合项目负责人之间的研究工作，以确定潜在的疫苗抗原，并促进最佳疫苗配方的开发。

Despite innate limitations of animal models, the mouse model is a well established approximation of human candidiasis. In humans and mice, the kidneys are a target organ during pathogenesis of disseminated candidiasis and the fungus can migrate to the central nervous system in both types of mammals. Vaginal and intestinal mucosal infections can be established in the mouse and mechanisms of hot resistance at these sites may be similar to humans. Macrophage and neutrophil interactions and candidacidal activities of these cell types are at similar levels for cells isolated from mouse and man. The mouse can also be used as a starting point to predict the efficacy of anti-candida drugs in humans. These advantages along with choices of many kinds of inbred and outbred strains of mice, various relevant gene knockout mice, and the available repertoire of chemical and immunologic regents make the mouse model of candidiasis very responsible for identification of candidate antigens to be used in a vaccine regimen. Mice and rabbits will be used as develop to develop polyclonal antibodies against the various vaccine candidate antigens originating from the Cutler, Edwards, and Mitchell projects of the MRU. Mouse polyclonal antisera will be used in passive transfer experiments to determine if an antibody against a particular antigen preparation confers resistance against candidiasis in naive mice. We have had extensive experience in this kind of evaluation. Rabbits will be used to prepare large amounts of antisera against a candidate antigen for the purpose of affinity purification, localization of specific antigens on or in yeast cells, function blocking experiments, and other applications as appropriate. The Animal Core provides support services for all four projects. Specifically the Core will: i.). Assist each Project Leader in the development, design and evaluation of experiments for determining the in vivo efficacy of vaccine formulations and antibodies against experimental candidiasis in normal and neutropenic mice. ii) raise mouse and rabbit polyclonal antibodies against various Candida vaccine candidate antigens, and against peptides that mimic such antigens, as [provided by each Project Leader. iii.) Integrate the research efforts between the Project Leaders to identify potential vaccine antigens and facilitate development of the best possible vaccine formulations.