Pamungkas, JokoDe Rose, RobertIskandriati, DiahNoviana, RachmitasariParamastri, YasminaDale, C JaneShoobridge, MaryanneMedveczky, CRamshaw, IanThomson, ScottKent, Stephen J2015-12-130889-2229http://hdl.handle.net/1885/81934T cell immunity plays a critical role in controlling HIV-1 viremia, and encoding a limited set of HIV-1 genes within DNA and poxvirus vectors can, when used sequentially, induce high levels of T cell immunity in primates. However, a limited breadth of T cell immunity exposes the host to potential infection with either genetically diverse HIV-1 strains or T cell escape variants of HIV-1. In an attempt to induce maximally broad immunity, we examined DNA and recombinant fowlpox virus (rFPV) vaccines encoding all HIV-1 genes derived from a global HIV-1 consensus sequence, but expressed as multiple overlapping scrambled 30-amino acid segments (scrambled antigen vaccines, or SAVINEs). Three groups of seven pigtail macaques were immunized with sets of DNA and rFPV expressing Gag/Pol antigens only, the whole genome SAVINE antigens, or no HIV-1 antigens and T cell immunity was monitored by ELISpot and intracellular cytokine staining. High levels of cross-subtype HIV-specific T cell immunity to Gag were consistently induced in the seven macaques primed with DNA and rFPV vaccines expressing Gag/Pol as intact proteins. It was, however, difficult to repeatedly boost immunity with further rFPV immunizations, presumably reflecting high levels of anti-FPV immunity. Unfortunately, this vaccine study did not consistently achieve a broadened level of T cell immunity to multiple HIV genes utilizing the novel whole-virus SAVINE approach, with only one of seven immunized animals generating broad T cell immunity to multiple HIV-1 proteins. Further refinements are planned with alternative vector strategies to evaluate the potential of the SAVINE technology.Keywords: antigen p24; DNA vaccine; Fowlpox virus vaccine; Gag protein; gamma interferon; Human immunodeficiency virus vaccine; Pol protein; recombinant vaccine; scrambled antigen vaccine; unclassified drug; amino acid sequence; animal cell; animal experiment; anti200510.1089/aid.2005.21.2922015-12-11