IMMUNE FUNCTION AND BIODEFENSE IN CHILDREN, ELDERLY, AND COMPROMISED POPULATIONS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Risk of encephalitis from West Nile virus (WNV) infection increases dramatically with age. Individuals suffering neuroinvasive illness have mortality rates of less than 4% if under the age of 70, after which rates rise to over 20%. Our collaborators at ONPRC challenged sixteen age rhesus macagues (17-30 yrs) and 9 adult Rhesus (6-9 yrs) with two does of virus (1 x 107 or 1 x 109 pfu/animal); some experiments included mosquito salivary gland extract (SGE) generated from the insectory at TNPRC. Additionally fifteen Cynomolgus monkeys were challenged after thymectomy and/or CD8 T cell depletion to test various levels of immunodeficiency. Animals remained clinically normal. No fever, change in appetite, or behavior was detected that could be attributed to WNV infection. Quantitative PCR of whole blood revealed discrete and short lived viremia; however infectious virus was never isolated. Analysis of innate immune response revealed a marked increase in monocytes and eosinophils (with SGE) between days 2 and 10 post infection. Additionally flow cytometric analysis of PBMC revealed increased proliferation of CD3- cells. With regard to adaptive immunity, an age-associated reduction in CD4+ T cell proliferation was found. Humoral responses developed and were detected in nearly all animals. The results suggest that non-human primates mount and maintain an effective innate defense to WNV challenge. This project ended in June, 2010 and results were published in December.