Functionally-inactive and immunogenic Tat, Rev and Nef DNA vaccines derived from sub-Saharan subtype C human immunodeficiency virus type 1 consensus sequences

• Published in: Vaccine Vol. 23; no. 9; pp. 1158 - 1169
• Main Authors: Scriba, Thomas J., zur Megede, Jan, Glashoff, Richard H., Treurnicht, Florette K., Barnett, Susan W., van Rensburg, Estrelita Janse
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 19.01.2005; Elsevier; Elsevier Limited
• Subjects: Acquired immune deficiency syndrome; AIDS; AIDS Vaccines - genetics; AIDS Vaccines - immunology; Animals; Applied microbiology; Biological and medical sciences; Cell Line; Consensus Sequence - immunology; DNA vaccine; Female; Fundamental and applied biological sciences. Psychology; Genes, nef - genetics; Genes, nef - immunology; Genes, rev - genetics; Genes, rev - immunology; Genes, tat - genetics; Genes, tat - immunology; HeLa Cells; HIV; HIV-1; HIV-1 - genetics; HIV-1 - immunology; Human immunodeficiency virus; Human immunodeficiency virus 1; Human viral diseases; Humans; Infectious diseases; Medical sciences; Mice; Mice, Inbred BALB C; Microbiology; Miscellaneous; Mutation; Regulatory genes; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, DNA - classification; Vaccines, DNA - genetics; Vaccines, DNA - immunology; Vaccines, Inactivated - genetics; Vaccines, Inactivated - immunology; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Virology; Sub-Saharan Africa; HIV-1; DNA vaccine; Regulatory genes; Immunopathology; HIV-1 virus; Consensus sequence; Retroviridae; AIDS; Genetic vaccine; Immune deficiency; Lentivirus; Infection; Virus; Immunogenicity; Viral disease; Human immunodeficiency virus; Subtype
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2004.08.026

The efficacy of cellular immune responses elicited by HIV vaccines is dependent on their strength, durability and antigenic breadth. The regulatory proteins are abundantly expressed early in the viral life cycle and CTL recognition may bring about early killing of infected cells. We synthesised DNA vaccine constructs that encode consensus HIV-1 subtype C Tat, Rev and Nef proteins. Proteins carrying inactivating mutations were tested for functional activity and highly expressing, inactive Tat, Rev and Nef mutants were identified and their reading frames fused into a TatRevNef cassette. Single- and polygene Tat, Rev and/or Nef constructs were immunogenic in BALB/c mice. These constructs may serve to increase the antigenic breadth for an HIV-1 vaccine that is relevant for sub-Saharan Africa.