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.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
2P51RR000165-51
Application #
8357411
Study Section
Special Emphasis Panel (ZRR1-CM-5 (01))
Project Start
2011-08-01
Project End
2012-04-30
Budget Start
2011-08-01
Budget End
2012-04-30
Support Year
51
Fiscal Year
2011
Total Cost
$74,294
Indirect Cost
Name
Emory University
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
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Furlan, Scott N; Watkins, Benjamin; Tkachev, Victor et al. (2016) Systems analysis uncovers inflammatory Th/Tc17-driven modules during acute GVHD in monkey and human T cells. Blood 128:2568-2579
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Masilamoni, Gunasingh J; Uthayathas, Subramanian; Koenig, Gerhard et al. (2016) Effects of a novel phosphodiesterase 10A inhibitor in non-human primates: A therapeutic approach for schizophrenia with improved side effect profile. Neuropharmacology 110:449-57
Singh, Arun; Mewes, Klaus; Gross, Robert E et al. (2016) Human striatal recordings reveal abnormal discharge of projection neurons in Parkinson's disease. Proc Natl Acad Sci U S A 113:9629-34
Michopoulos, Vasiliki (2016) Stress-induced alterations in estradiol sensitivity increase risk for obesity in women. Physiol Behav 166:56-64
Honegger, Jonathan R; Tedesco, Dana; Kohout, Jennifer A et al. (2016) Influence of IFNL3 and HLA-DPB1 genotype on postpartum control of hepatitis C virus replication and T-cell recovery. Proc Natl Acad Sci U S A 113:10684-9

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