IMMUNE FUNCTION AND BIODEFENSE IN CHILDREN, ELDERLY, AND THE IMMUNOCOMPROMISED

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 该项目的近期目标是建立西尼罗河病毒(WNV)感染和恒河猴(RM)免疫的模型，长期目标是开发一种改进的、更安全的疫苗来对抗西尼罗河病毒引起的老年发病率和死亡率。虽然不只是一种老年人的疾病，但似乎老年人由于免疫系统能力下降而面临更大的风险。我们将测试老化的免疫反应是否缺乏成熟完整的免疫系统的特征，并确定蚊子是否贡献了抑制西尼罗河病毒免疫反应的成分。最初，自然暴露于西尼罗河病毒的17岁以上恒河猴的细胞免疫功能将与正常暴露的成年猴子进行比较。随后，将在ONPRC进行有无蚊子成分的西尼罗河病毒感染，以评估蚊子对疾病传播和病毒持久性的免疫学和病理学影响。对感染细胞和细胞免疫参与者的识别将识别老年人中的脆弱细胞靶点，这些靶点可能是持续感染的重要来源、诊断哨点和治疗目标。来自TNPRC的20只老年恒河猴和12只成年对照猴子的免疫学特征正在进行中，ONPRC的小鼠感染研究和树突状细胞实验仍在继续。唾液腺的活体提取和导入实验以及猴子感染研究计划在该项目的第二年进行。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The immediate goal of this project is to develop a model of West Nile virus (WNV) infection and immunity in rhesus macaques (RM) with a long term goal of developing an improved and safer vaccine against WNV induced morbidity and mortality in the elderly. Although not exclusively a disease of the aged, it appears that older individuals may be more at risk due to declining capabilities of their immune systems. We will test whether the aged immune response lacks features of a mature intact imune system and determine if the mosquito contributes components that suppress immune response to WNV. Initially cellular immune function of rhesus monkeys greater than 17 years of age that were naturally exposed to WNV will be compared to normal exposed adult monkeys. Later WNV infection will be done at ONPRC with and without mosquito components to assess the immunologic and pathologic effects of the mosquito on disease transmission and viral persistence. Identification of infected cells and cellular immune participants will identify vulnerable cellular targets in aged individuals that may be important as sources of persistent infection, diagnostic sentinels and targets of therapy. Immunological characterization of 20 aged rhesus monekys and 12 adult control monkeys from TNPRC is in progress and murine infection studies and dendritic cell experiments continue at ONPRC. Salivary gland extract in vivo and intro experiments and monkey infection studies are scheduled for year 2 of this project.