GB VIRUS C INFECTION OF MACAQUES: AN HIV VACCINE MODEL

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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. An estimated 40 million persons are infected with HIV, which caused more than three million deaths in 2001 alone. Efforts to prevent HIV infection by vaccination have no been successful, in large part because of the limited efficacy of conventional vaccine constructs as well as concerns with the safety of live virus vectors. To overcome these limitations, we propose using GB virus C, a recently discovered flavivirus, as a recombinant vector for HIV vaccines. GBV-C has many features of an ideal recombinant vector including: Safety 9No known human disease is associated with this virus which causes persistent infection in ~2% of healthy blood donors and, although transmitted by transfusion, is not screened for in donations.); experimental models (Cell lines exist for GBV-C and an infectious clone has already been made. In addition, there is evidence that macaques, the most important animal model for HIV vaccine research, are permissive for GBV-C.); and immunogenicity (Strong cellular and humoral immune responses are expected since the virus infects humans for months/decades.). Thus, the purpose of this pilot grant is to conduct preliminary studies required for expanded work to develop GBV-C as a recombinant vector for HVI vaccines. Our initial aims are to confirm that rhesus macaques can be infected with GBV-C, to characterize the natural history of infection, and to provisionally examine tissue tropism.