1. Comparison of whole gene and whole virus scrambled antigen approaches for DNA prime and fowlpox virus boost HIV type 1 vaccine regimens in macaques.
- Author
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Pamungkas J, De Rose R, Iskandriati D, Noviana R, Paramastri Y, Dale CJ, Shoobridge M, Medveczky CJ, Ramshaw IA, Thomson S, and Kent SJ
- Subjects
- AIDS Vaccines administration & dosage, Animals, Consensus Sequence, Cross Reactions, HIV Antibodies blood, HIV Antigens genetics, HIV Antigens immunology, HIV Core Protein p24 immunology, HIV Infections prevention & control, Immunity, Cellular, Immunization, Secondary, Interferon-gamma biosynthesis, Lymphocyte Count, Macaca nemestrina, Models, Animal, Vaccines, DNA administration & dosage, Vaccines, Synthetic genetics, Vaccines, Synthetic immunology, AIDS Vaccines immunology, Fowlpox virus immunology, T-Lymphocytes immunology, Vaccines, DNA immunology
- Abstract
T 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.
- Published
- 2005
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