Histologic Markers of Resistance to Coccidioidomyoosis

球孢子菌病抗性的组织学标志物

• 批准号: 7629174
• 负责人: JOHN N GALGIANI
• 金额: $ 10.7万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7629174
• 关键词: Adjuvant; Antigens; Appearance; Bronchoalveolar Lavage Fluid; C57BL/6 Mouse; Cellular Immunity; Characteristics; Clinical; Clinical Trials; Coccidioides; Coccidioidomycosis; Condition; Conflict (Psychology); Drug Formulations; Effector Cell; Exposure to; Formalin; Future; Genetic; Histologic; Histopathology; Human; Immune; Immune response; Immunity; Immunologics; In Situ Hybridization; Inbred DBA Mice; Inbred Strains Mice; Infection; Lesion; Lung; Mass Spectrum Analysis; Membrane; Methods; Mus; Operative Surgical Procedures; Outcome; Patients; Pattern; Predisposition; Proteins; Protocols documentation; Recombinants; Resistance; Resistance to infection; Specimen; Staining method; Stains; Structure of parenchyma of lung; T-Lymphocyte Subsets; Testing; Time; Tissues; Two-Dimensional Polyacrylamide Gel Electrophoresis; Vaccinated; Vaccination; Vaccines; Validation; Whole Cell Vaccine; base; cell type; cytokine; improved; killings; prevent; response; vaccine efficacy

Current methods for assessing vaccine candidates for preventing coccidioidomycosis yield different results with different test conditions, limiting their usefulness. To improve this situation, this project will first develop histopathologic profiles of host response to infection in the lungs of genetically resistant mice (DBA), both naive and FKS vaccinated, and compare this profile to the response in FKS vaccinated and unvaccinated genetically susceptible mice (C57BL/6). Immunohistochemical stains for cell-type specific membrane markers and cytokines will be applied to lung tissue over a time course following infection. The results will guide selected analyses of bronchoalveolar lavage fluid (BALF) by 2D PAGE and mass spectrometry to identify additional proteins associated with resistance and guide additional analyses of tissue by in situ hybridization with cytokine probes. These pulmonary responses for susceptible and resistant mice will be compared to those produced by recombinant antigens in various vaccination protocols. These analyses should identify vaccine formulations and protocols that result in histologic patterns closest to those found with resistance, either genetic or FKS-produced. In addition, this project will draw comparisons between the pulmonary histopathology of experimental murine infections and histologic material from human surgical specimens obtained during local clinical practice.

当前评估候选疫苗预防球菌病的方法产生不同的结果 在不同的测试条件下，限制了它们的实用性。为了改善这种情况，该项目将首先发展 遗传抗性小鼠肺（DBA）宿主反应的组织病理学特征，两者均 幼稚和FKS接种疫苗，并将此轮廓与FKS接种疫苗接种的响应进行比较 遗传易感小鼠（C57BL/6）。细胞型特异性膜的免疫组织化学染色 感染后的时间过程中，标记和细胞因子将在肺组织中应用。结果将 指南对支气管肺泡灌洗液（BALF）的选定分析，分别是2D页，质谱分析 确定与耐药性相关的其他蛋白质，并在原位指导组织的其他分析 与细胞因子探针杂交。这些对易感和抗性小鼠的肺反应将是 与重组抗原在各种疫苗接种方案中产生的抗原产生的抗原相比。这些分析 应确定导致最接近发现的组织学模式的疫苗配方和协议 具有遗传或FKS产生的抗性。此外，该项目将在 实验性鼠感染和组织学材料的肺部组织病理学 在当地临床实践中获得的标本。