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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。该项目的近期目标是在恒河猴（RM）中建立西尼罗河病毒（WNV）感染和免疫模型，长期目标是开发一种改进的和更安全的疫苗，以防止西尼罗河病毒在老年人中引起的发病率和死亡率。虽然这不是老年人特有的疾病，但由于免疫系统能力的下降，老年人可能面临更大的风险。我们将测试老年免疫反应是否缺乏成熟完整免疫系统的特征，并确定蚊子是否提供抑制西尼罗河病毒免疫反应的成分。首先将17岁以上自然暴露于西尼罗河病毒的恒河猴的细胞免疫功能与正常暴露于西尼罗河病毒的成年猴子进行比较。随后将在ONPRC进行有和没有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和病理影响。识别感染细胞和细胞免疫参与者将识别老年人的脆弱细胞靶标，这些靶标可能是重要的持续性感染源、诊断哨兵和治疗靶标。

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 immune 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.