IMMUNE RESPONSE TO COCCIDIOIDES IMMITIS PROLINE RICH ANTIGEN

描述(改编自应用程序)：调查人员建议分析 重组富含脯氨酸抗原(PRA)的免疫原性差异 它的长度。基于对其他T细胞刺激抗原的分析 包括二相性真菌组织胞浆菌在内的其他几种病原体 和巴西副球藻Paracoccidioidesbrasiliens，预计存在 免疫优势。在某些情况下，抗原性可以映射到特定的 表位。对免疫反应部位的准确了解可能会 通过去除抑制物或有毒物质来提高疫苗效力 来自候选疫苗的分子的一部分。此外，确定 PRA的最小有效单位将增加更多 包括在多价疫苗策略中的抗原。具体目标为 该项目将是：1)表征全长PRA的保护 关于近交系小鼠的疫苗剂量、佐剂要求和范围；2) 比较四个跨越PRA全长的重组重叠多肽 针对生产保护中的差异和相互作用；3)地图 利用人工合成的寡肽对PRA特定象限的免疫反应性 作为疫苗接种引起的免疫的探针。在与 关于保护的研究，调查人员将检查 观察保护的替代标记。将选择免疫学测试 与未来的人类疫苗试验的实际相关性，并将包括 淋巴细胞转化、细胞因子产生对抗原的反应 刺激和足垫肿胀作为延迟型的指标 过敏症。最后，调查人员计划延长他们的评估 PRA具有预防鼻腔感染的能力，这是 从历史上看，疫苗被视为对疫苗效力的更严格测试。

DESCRIPTION (Adapted from application): The investigators propose to analyze recombinant proline-rich antigen (PRA) for differences in immunogenicity along its length. Based on analyses of other T cell-stimulating antigens from several other pathogens including the dimorphic fungi Histoplasma capsulatum and Paracoccidioides brasiliensis, it is anticipated that there exist regions of immunodominance. In some cases, antigenicity can be mapped to specific epitopes. A precise understanding of the location of immunoreactivity could lead to improved vaccine effectiveness by removing inhibitory or toxic portions of the molecule from the vaccine candidate. Furthermore, determining the smallest effective unit of PRA would increase the feasibility for more antigens to be included in a multivalent vaccine strategy. Specific aims for this project will be: 1) characterize protection of the full length PRA with respect to vaccine dose, adjuvant requirements, and range of inbred mouse; 2) compare four recombinant overlapping peptides that span the full length of PRA for differences and interactions in producing protection; 3) map immunoreactivity of a specific quadrant of PRA using synthetic oligopeptides as probes of immunization resulting from vaccination. In parallel to the studies of protection, the investigators will examine the correlation of surrogate markers to observed protection. Immunologic tests will be selected for their practical relevance to future human vaccine trials and will include lymphocyte transformation, cytokine production in response to antigenic stimulation, and footpad swelling as an indicator of delayed-type hypersensitivity. Finally, the investigators plan to extend their evaluation of PRA to its capacity to protect against intranasal infection, which historically has been viewed as a more stringent test of vaccine potency.