Recombinant fowlpoxvirus expressing HIV gag-pol antigens vaccine(Virax Pty)

To induce broad T cell immunity to HIV-1, we evaluated the safety, immunogenicity and dose-response relationship of DNA and recombinant Fowlpoxvirus (rFPV) vaccines encoding five shared HIV subtype AE genes (Gag, Pol, Env, Tat, Rev) in pigtail macaques. The DNA (three doses of either 1 mg or 4.5 mg) and rFPV (a single boost of either 5 x 10(7) or 2 x 10(8) plaque forming units) vaccines were administered intramuscularly without adjuvants. Broadly reactive HIV-specific T cell immunity was stimulated by all doses of the vaccines administered, without significant differences between the high and low doses studied. The vaccines induced both CD4 and CD8 T cell responses to Gag, Pol, Env and Tat/Rev proteins, with CD4 T cell responses being greater in magnitude than CD8 T cell responses. The vaccine-induced T cell responses had significant cross-recognition of heterologous HIV-1 proteins from non-AE HIV-1 subtypes. In conclusion, these subtype AE HIV-1 DNA and rFPV vaccines were safe, induced broad T-cell immunity in macaques, and are suitable for progression into clinical trials.

Induction of HIV-specific T-cell responses by vaccines may facilitate efficient control of HIV. Plasmid DNA vaccines and recombinant fowlpoxvirus (rFPV) vaccines are promising HIV-1 vaccine candidates, although either vaccine alone may be insufficient to protect against HIV-1. A consecutive immunisation strategy involving priming with DNA and boosting with rFPV vaccines encoding multiple common HIV-1 antigens was further evaluated in 30 macaques. The DNA vaccine vector included CpG immunostimulatory molecules, and rFPV vaccines were compared with rFPV vaccines co-expressing the pro-T cell cytokines IFNgamma or IL-12. Vaccines expressed multiple HIV-1 genes, mutated to remove active sites of the HIV proteins. The vaccines were well tolerated, and a significant enhancement of DNA-vaccine primed HIV-1 specific T lymphocyte responses was observed following rFPV boosting. Co-expression of IFNgamma or IL-12 by the rFPV vaccines did not further enhance immune responses. Non-sterilising protection from a non-pathogenic HIV-1 challenge was observed. This study provides evidence of a safe, optimised, strategy for the generation of T-cell mediated immunity to HIV-1.