Construction and characterisation of a candidate HIV-1 subtype C DNA vaccine for South Africa.
A candidate DNA vaccine pTHgagC expressing the immunodeficiency virus-1 (HIV-1) gag gene from South African isolate Du422 was constructed and characterised. The isolate was selected on the basis of being the closest to the South African subtype C consensus sequence. Sequence analysis of cytotoxic T lymphocyte (CTL) epitopes showed that HIV subtype C-infected individuals have CTL responses to a number of epitopes present in the vaccine, but also revealed a more limited presence of subtype A- and any B-derived epitopes. A high level of expression of the immunogen was demonstrated in human cells and a potent, long-lived CTL response to a single inoculation of the DNA vaccine was elicited in BALB/c mice, which could be significantly increased by a boost vaccination at 4 weeks. This is the first candidate HIV-1 DNA vaccine employing the South African subtype C sequences, and constitutes a part of a vaccine scheduled to enter a clinical evaluation in South Africa in 2004.
D016915:AIDS Vaccines / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D002860:Chromium Radioisotopes; D003601:Cytotoxicity Tests, Immunologic; D018076:DNA, Complementary / Q000276:immunology*; D015750:Genes, gag / Q000235:genetics; D015497:HIV-1 / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D013019:South Africa; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology
D016915:AIDS Vaccines; D002860:Chromium Radioisotopes; D018076:DNA, Complementary; D019444:Vaccines, DNA; D007371:Interferon-gamma