IMMUNE RESPONSE TO COCCIDIOIDES IMMITIS PROLINE RICH ANTIGEN

对犬球孢子菌脯氨酸富集抗原的免疫反应

• 批准号: 6657470
• 负责人: JOHN N GALGIANI
• 金额: $ 15.71万
• 依托单位: VETERANS MEDICAL RESEARCH FDN/SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6657470
• 关键词: Coccidioides immitis; coccidioidomycosis; cytokine; delayed hypersensitivity; disease /disorder model; dosage; drug administration routes; epitope mapping; fungal antigens; fungal vaccines; genetic strain; laboratory mouse; leukocyte activation /transformation; proline; protein biosynthesis; recombinant proteins; synthetic peptide; vaccine development

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.

描述（改编自应用程序）：研究者建议分析 重组富脯氨酸抗原（PRA）的免疫原性差异，沿着 它的长度。基于对来自其他T细胞刺激抗原的分析， 其他几种病原体，包括二型真菌荚膜组织胞浆菌 和Paracoccidioides brasiliensis，预计存在区域 免疫优势在某些情况下，抗原性可以映射到特定的 表位精确了解免疫反应性的位置可以 通过去除抑制性或毒性而导致改进疫苗效力 来自候选疫苗的分子部分。此外，确定 PRA的最小有效单位将增加更多的可行性， 抗原被包括在多价疫苗策略中。具体目标 该项目将：1）描述保护全长PRA的特征， 关于疫苗剂量、佐剂要求和近交系小鼠范围; 2） 比较四种跨越PRA全长的重组重叠肽， 生产保护的差异和相互作用; 3）地图 使用合成寡肽对PRA特定象限的免疫反应性 作为疫苗接种产生的免疫探针。平行于 保护的研究，调查人员将研究的相关性， 替代标记物来观察保护作用。将选择免疫学检查 它们对未来人类疫苗试验的实际意义，并将包括 淋巴细胞转化，细胞因子的产生 刺激和足垫肿胀作为延迟型的指标 超敏反应最后，研究人员计划将他们的评估 PRA的能力，以防止鼻内感染， 在历史上被认为是对疫苗效力的更严格的测试。