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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.

Type

Journal article

Journal

Vaccine

Publication Date

01/10/2003

Volume

21

Pages

4380 - 4389

Keywords

AIDS Vaccines, Amino Acid Sequence, Animals, Chromium Radioisotopes, Cytotoxicity Tests, Immunologic, DNA, Complementary, Genes, gag, HIV-1, HeLa Cells, Humans, Immunization, Interferon-gamma, Mice, Mice, Inbred BALB C, Molecular Sequence Data, South Africa, T-Lymphocytes, Regulatory, Vaccines, DNA