IN SITU GENE-MODIFIED DCS FOR AN HIV-1 T CELL VACCINE

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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. Although protective vaccination strategies have been developed against many infectious diseases of viral origin, a vaccine with broad activity against HIV-1 has remained elusive for two decades. Cell-mediated immunity has been implicated in (i) modulation of HIV-1 replication, (ii) protraction of disease progression, and (iii) protection against infection, arguing their importance as components of a successful immunization strategy. Dendritic cells (DC) can present antigens via MHC class I and II pathways and are central to the development of cell-mediated immune responses. Thus, DC-based vaccines are currently being developed as agents to elicit strong, antigen-specific T cell responses, but these protocols usually require ex vivo genetic modification of DCs, followed by re-infusion back into an autologous or MHC-matched host where they mature, migrate to lymph nodes, and present the candidate antigen to CD4 and/or CD8 T cells to elicit antigen-specific responses. Although the ex vivo genetic manipulation approach has been useful in establishing proof-of-concept in an experimental setting, it is not practical for the development of prophylactic vaccines to be used in the field. If transduction of the DCs could be accomplished in situ, the broad use of DC-targeted vaccines as prophylactic agents would be more feasible.