NOVEL ADENOVIRUS-VECTORED HIV VACCINE THAT KNOCKS THE SOCS1 OFF DENDRITIC CELLS

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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. Antigen-presenting cells, such as DCs, play a critical role in the establishment and maintenance of the immune responses against HIV infection; DCs are key targets for vaccines that stimulate immune signaling. We have made the following progress during this funding period: + Developed panel of adenovirus-based vectors that co-express (i) SOCS1 siRNA and (ii) the reporter gene Green Fluorescent Protein (GFP) or antigen gene HIV-1 gag. + Have tested effects of SOCS1 siRNA on dendritic cell phenotype. No negative effects on dendritic cell maturation were observed. + Developed a Western blot approach for detecting the effects of SOCS1 siRNA expression on the phosphorylation of STAT1 following INF-gamma stimulation as a surrogate measurement of SOCS1 siRNA-silencing. The results from these experiments suggest that our SOCS1 siRNA-expressing vectors enhance the STAT1 signaling pathway and support our hypothesis. Significance: Development of a novel adenovirus vector platform that is designed to directly modulate the immune responses induced by the vaccine. Moreover, the work thus far suggests that attenuating the down-regulatory role of SOCS1 during the induction of immune responses will serve to significantly improve vaccine efficacy.