CORE--ANIMAL

核心--动物

• 批准号: 6134338
• 负责人: Jim E. Cutler
• 金额: $ 16.7万
• 依托单位: LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-15 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6134338
• 关键词: animal care; antiserum; biomedical facility; candidiasis; laboratory mouse; laboratory rabbit

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.

尽管动物模型的先天局限性，小鼠模型是人类念珠菌病的一个很好的近似建立。在人类和小鼠中，肾脏是播散性念珠菌病发病过程中的一个目标器官，真菌可以迁移到这两种哺乳动物的中枢神经系统。阴道和肠道粘膜感染可以在小鼠中建立，这些部位的热抗性机制可能与人类相似。巨噬细胞和中性粒细胞的相互作用以及这些细胞类型的候选菌活性在小鼠和人分离的细胞中处于相似的水平。小鼠也可以作为一个起点，预测抗念珠菌药物对人类的疗效。这些优势，加上多种近交系和远交系小鼠的选择，各种相关基因敲除小鼠，以及可用的化学和免疫试剂，使念珠菌病小鼠模型非常负责鉴定用于疫苗方案的候选抗原。小鼠和家兔将作为研究对象，开发针对MRU Cutler、Edwards和Mitchell项目中各种候选疫苗抗原的多克隆抗体。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的抗体是否能在幼稚小鼠中对念珠菌病产生抗性。我们在这种评估方面有丰富的经验。兔将被用来制备大量针对候选抗原的抗血清，用于亲和纯化、酵母细胞上或酵母细胞内特异性抗原的定位、功能阻断实验和其他适当的应用。动物中心为这四个项目提供支持服务。具体来说，核心将：i.)。协助每个项目负责人进行实验的开发、设计和评估，以确定正常和中性粒细胞减少小鼠体内抗实验性念珠菌病的疫苗配方和抗体的有效性。ii)培养针对各种假丝酵母疫苗候选抗原的小鼠和兔多克隆抗体，以及针对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]。iii)。整合项目领导人之间的研究工作，以确定潜在的疫苗抗原，并促进开发尽可能最佳的疫苗配方。