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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A variety of viral vectors have been employed to accomplish gene-based vaccination. One particularly promising approach is based upon genetic transduction via replication-incompetent adenoviral vectors (Ad). Despite the many potential advantages of Ad vectors for vaccine application, full utility of current Ad vaccines may be limited by the host anti-vector immune response. Specifically, the anti-Ad humoral immunity abrogates the effectiveness of subsequent administrations of the Ad vector, confounding expression of the encoded transgene, and thus practically restricting the gains that might be accrued via booster effect. To exploit the inherent antigenicity of the Ad vector we have developed an approach based on incorporation of the immunizing antigen epitope directly into the Ad capsid. This novel paradigm is based upon Ad presenting the antigen as a component of the capsid rather than an encoded transgene. Incorporation of immunogenic peptides into the Ad capsid offers potential advantages. Most noteworthy, the processing of the capsid incorporated antigen via the exogenous pathway should result in a strong humoral response akin to the response provoked by native Ad capsid proteins. In addition, since anti-Ad capsid responses are augmented by repeated vector administration, immune responses against antigenic epitopes that are part of the Ad capsid should be augmented by repeated administration as well, thus allowing boosting. These considerations suggest that this novel capsid-incorporated antigen approach may offer exciting potentials to realize Ad-based vaccine strategies that circumvent the major limitations associated with Ad vectors.