HUMAN IMMUNE RESPONSES TO YELLOW FEVER VIRUS

人类对黄热病病毒的免疫反应

• 批准号: 6038128
• 负责人: Sharone Green
• 金额: $ 11.75万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6038128
• 关键词: Flaviviridae; cellular immunity; clinical research; cytotoxic T lymphocyte; dengue virus; human subject; immunologic memory; neutralizing antibody; recombinant virus; viral vaccines; virus antigen; virus load; yellow fever

DESCRIPTION (adapted from application abstract): Yellow fever virus (YF) infections are an important and emerging health problem in Africa and South America, despite the availability of the licensed, safe and immunogenic YF 17D strain vaccine. Little is known about the cellular immune responses to YF or the mechanism of pathogenesis in humans. T lymphocyte studies in a related human flavivirus, dengue, have demonstrated that CD4+ and CD8+ memory T cells are generated with the nonstructural NS3 protein as an immunodominant protein. Recently chimaeric flaviviruses have been developed with a YF nonstructural gene as a backbone for Japanese encephalitis (JE) structural genes. These new vaccines will soon enter Phase I clinical trials and further emphasize the importance of learning more about human immune responses to YF. There are two major goals presented training and research in human immune responses to yellow fever virus. To achieve the first goal training a two-year curriculum involving didactic training in biochemistry, molecular biology, cellular and molecular immunology, biostatistics and epidemiology. Laboratory rotations will complement didactic studies in the area of molecular biology. The candidate will learn (1) to construct a vaccines/YF NS3 recombinant virus; (2) to design primers to develop a qualitative nested RT-PCR for the detection of YF RNA in human primate specimens; (3) to create a competitor for the development of a quantitative competitor RT-PCR for the titration of YF RNA; (4) to engineer a YF/dengue chimaeric virus. The molecular reagents developed above will be utilized in the Research Plan. The specific aims are: (1) to define the immunodominant proteins recognized by T lymphocytes in TF- vaccinated individuals; (2) To examine viral replication by quantitative RT- PCR during primary infection/vaccination and its relationship to clinical and/or immunological outcome; (3) To determine if a correlation exists between the pre-existing level of memory cytotoxic T lymphocyte response or neutralizing antibody responses and the development of subsequent viremia, neutralizing antibody responses and/or cellular immune responses following administration of a second dose of YF or chimaeric YF/JE vaccine.

描述（改编自申请摘要）：黄热病病毒（YF） 感染是非洲和南部地区一个重要且新出现的健康问题 美国，尽管可以获得许可、安全且具有免疫原性的 YF 17D 毒株疫苗。 对于 YF 或 YF 的细胞免疫反应知之甚少 人类发病机制。 相关T淋巴细胞研究 人类黄病毒、登革热已证明 CD4+ 和 CD8+ 记忆 T 细胞 由作为免疫显性蛋白的非结构 NS3 蛋白生成。 最近，已开发出具有 YF 非结构性嵌合黄病毒 基因作为日本脑炎（JE）结构基因的主干。 这些新 疫苗即将进入一期临床试验，进一步强调 了解更多有关 YF 的人类免疫反应的重要性。 有两个 主要目标是人类免疫反应的培训和研究 黄热病病毒。 为实现第一个目标训练两年 课程涉及生物化学、分子生物学的教学培训， 细胞和分子免疫学、生物统计学和流行病学。 实验室 轮换将补充分子生物学领域的教学研究。 考生将学习 (1) 构建疫苗/YF NS3 重组病毒； (2) 设计引物开发定性巢式RT-PCR检测 人类灵长类动物标本中的 YF RNA； (3) 创造竞争者 开发用于 YF RNA 滴定的定量竞争性 RT-PCR； (4)设计YF/登革热嵌合病毒。 开发的分子试剂 以上将在研究计划中使用。具体目标是：（1） 定义 TF- 中 T 淋巴细胞识别的免疫显性蛋白 已接种疫苗的个人； (2) 通过定量RT-检查病毒复制 原发感染/疫苗接种过程中的PCR及其与临床的关系 和/或免疫学结果； (3) 判断之间是否存在相关性 先前存在的记忆细胞毒性 T 淋巴细胞反应水平或 中和抗体反应和随后病毒血症的发展， 中和抗体反应和/或细胞免疫反应 施用第二剂 YF 或嵌合 YF/JE 疫苗。