COCCIDIOIDES IMMITIS EVOLUTION AND VACCINE PRODUCTION

球孢子菌的进化和疫苗生产

• 批准号: 6657471
• 负责人: JOHN W. TAYLOR
• 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/6657471
• 关键词: Coccidioides immitis; biochemical evolution; fungal genetics; fungal vaccines; genetic polymorphism; genetic strain; genetic transcription; microorganism culture; microorganism growth; nucleic acid sequence; phenotype; protein sequence; vaccine development

DESCRIPTION (Adapted from application): As evolutionary mycologists, the investigators propose to contribute to the vaccine project by making sure that natural variation in the genotype of the pathogen is accounted for in vaccine development and testing as follows: 1) expand the search to find all genetically differentiated populations or genetically isolated species of C. immitis. Previous studies have focused on clinical isolates from the United States. To search for additional genetic variation, the investigators propose to use the protocols they developed using U.S. clinical isolates on isolates from Mexico, soil, and non-human mammals; 2) use C. immitis isolates representing the genetically distinct groups found in our expanded search to examine nucleotide and amino acid variation in proteins selected for vaccine development. Examination of the genes, and infection of the amino acid sequence, will alert the investigators to potential problems in the use of overly variable genes and proteins; 3) use the same collection of isolates to measure transcription levels for genes of proteins that are candidates for vaccine development. Low levels of transcription may foreshadow problems with vaccine development; 4) provide the same collection of isolates for vaccine testing in mice; and 5) seek phenotypic correlates of genotypic differences in the California and non-California C. immitis species and optimize a genotyping method to encourage clinicians to compare pathogen genotype and disease progress.

描述（改编自应用）：作为进化真菌学家， 研究人员建议通过确保 在疫苗中考虑了病原体基因型的自然变异 开发和测试如下：1）扩大搜索，找到所有 遗传分化种群或遗传隔离种C. 免疫系统。以前的研究集中在来自美国的临床分离株上 States.为了寻找更多的遗传变异，研究人员建议 使用他们开发的美国临床分离株的方案 从墨西哥，土壤，和非人类哺乳动物; 2）使用C.丝虫分离株 代表了在我们扩大的搜索中发现的遗传上不同的群体， 检查疫苗蛋白质中的核苷酸和氨基酸变异 发展基因的检测，氨基酸的感染 序列，将提醒研究者在使用中的潜在问题， 过度变异的基因和蛋白质; 3）使用相同的分离物集合， 测量蛋白质基因的转录水平， 疫苗研发。低水平的转录可能预示着 疫苗开发; 4）为疫苗提供相同的分离株集合 在小鼠中进行测试;以及5）寻找基因型差异的表型关联， 加州和非加州C.犬种和优化基因分型 鼓励临床医生比较病原体基因型和疾病的方法 中求进工作总