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. YF-17D is one of the most effective vaccines available, and induces neutralizing antibody for up to 30 years and robust CTL responses. Our recent work has started to provide exciting clues on its mechanism of action. + YF-17D potently activates the innate immune system and dendritic cells by signaling through multiple TLRs, including TLR 2, 7/8 and 9, which are expressed on, and in, distinct DC subsets Consistent with this, YF-17D utilizes multiple TLR adaptor proteins (MyD88, TIRAP) in activating dendritic cells. + Triggering TLR 7/8 and 9 induces the anti-viral cytokine IFN-alpha;in contrast, triggering TLR 4 induces abundant Th1 inducing cytokine, IL-12p70;emerging evidence suggests that triggering TLR 2 may induce Th2 cytokines. Consistent with this, YF-17D, which triggers multiple TLRs, appears to induce a broad spectrum of responses, including IFN-alpha from PDCs, IL-12 from mDCs, IL-10, and a mixed Th1/Th2 profile. + Injection of YF-17D into mice results in potent activation of multiple DC subsets, and up-regulation of costimulatory molecules. + The quality of adaptive immune response triggered by YF-17D, our strategy is to perform preliminary experiments in mice, using UF-17D which expresses the class I restricted OVA peptide SIINFEKL. Our data suggests that YF-OVA induces potent clonal expansion of OVA-specific CD8+ T cells that secrete IL-2, IFN-gamma, IL-4, IL-5 and IL-13 ?a mixed Th1/Th2 profile. This is consistent with the fact that YF-17D engages TLR 9, 7/8 (Th1 biasing), as well as TLR 2 (Th2 biasing). These studies could have implications for HIV/AIDS research.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Primate Research Center Grants (P51)
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Special Emphasis Panel (ZRR1-CM-5 (01))
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Emory University
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