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

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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.