**5. Comparison of DNA Vaccines between Two Initiatives in South Africa**

In 2000, a University of Cape Town (UCT)-based consortium headed by Prof. Anna-LiseWilliamson was awarded funds by the South African AIDS Vaccine Initiative (SAAVI) for the development of HIV-1C vaccines for South Africa. Two vaccines—designated SAAVI DNA-C2 and SAAVI MVA-C—were deemed suitable for human clinical trials [9,10]. The vaccines expressed a HIV-1 subtype C truncated envelope protein Du151 (gp150) and the polyprotein designated Grttn described above, consisting of translational fusions of HIV-1 subtype C Gag Du422, and modified reverse transcriptase (RT), Tat-, and Nef-encoding ORFs. The vector backbone utilized for the DNA vaccines contained the regulatory R region from the 5 long terminal repeat (LTR) of human T-cell leukemia virus type 1, which acts as a transcriptional and post-transcriptional enhancer [33]. Rhesus macaques were inoculated at weeks 0, 4, and 8 with 4 mg of SAAVI DNA-C2. No HIV-specific ELISPOT responses were detected following the DNA vaccinations (unpublished data). In a more recent study funded by the South African Medical Research Council Strategic Health Innovation Partnerships (SHIP), DNA vaccines expressing the SIV Gag and HIV-1 subtype C truncated envelope ZM109F.PB4 were constructed utilizing the pTHPcapR vector backbone (unpublished data). Rhesus macaques were inoculated, at weeks 0 and 4 with 1 mg of the DNA vaccines (four-fold lower dose). Four out of five macaques developed IFN-γ ELISPOT responses following stimulation with SIV Gag and HIV-1 subtype Env peptides. It should be noted that the antigens used in the SHIP vaccines have been designed to be more immunogenic than those used in the SAAVI vaccines and thus the improvement in the immune response cannot be solely attributed to the increased expression of the Gag and Env due to the inclusion of the porcine circovirus in the DNA vaccines. However, the SHIP DNA vaccines elicited a HIV-specific T cell response despite being administered at a four-fold lower dose than the SAAVI DNA-C2 vaccine.
