CORE--ANIMAL

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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.