EFFICACY OF TLR7 AGONIST FOR CHRONIC HCV INFECTION IN CHIMPANZEES

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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. This contract was designed to evaluate the efficacy of a TLR7 agonist in the chimpanzee model of chronic HCV infections. TLR7 is expressed predominantly in plasmacytoid dendritic cells and induces upon stimulation interferon-¿ and a variety of immunostimulatory cytokines. This study examined efficacy in three HBV chronically infected chimpanzees. The TLR7 agonist was given by oral dosing three times per week for a total of 3 weeks. Blood and liver samples were taken at several times and evaluated for reduction in viral RNA quantitative RT-PCR, induction of innate immune transcripts in PBMC and the liver by quantitative RT-PCR TaqMan assays, induction of cytokine levels in the serum by Luminex, and activation of lymphocyte subsets by Flow Cytometry. The animals were monitored closely for adverse events including complete blood counts and blood chemistries.