The hypothesis of this fellowship proposal is that lambda phage vectors can be used to elicit strong immune responses to HIV-1 antigens, and that these immune responses can be enhanced through specific modifications of the phage that influence cell entry and/or capsid uncoating within mammalian cells. It is also hypothesized that phage-based vector systems can be effectively combined with other vaccine modalities (DMA plasmids, mammalian virus vectors) to elicit optimal immune responses. These hypotheses will be tested using a biologically contained, novel lambda phage vector developed in the sponsor's laboratory. This system permits the high copy number surface display of modified derivatives of the major lambda phage coat protein (gpD);it will be used to conduct experimental aims that will test whether specific coat modifications can enhance the effectiveness of lambda phage-mediated gene transfer, and increase the immunogenicity of lambda phage vectors. Overall, the work proposed is expected to provide an outstanding training vehicle, while also advancing the science of HIV vaccine development.
|Volcy, Ketna; Dewhurst, Stephen (2009) Proteasome inhibitors enhance bacteriophage lambda (lambda) mediated gene transfer in mammalian cells. Virology 384:77-87|