Functionally-inactive and immunogenic Tat, Rev and Nef DNA vaccines derived from sub-Saharan subtype C human immunodeficiency virus type 1 consensus sequences.
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.
Scriba
Thomas J
TJ
The Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
zur Megede
Jan
J
Glashoff
Richard H
RH
Treurnicht
Florette K
FK
Barnett
Susan W
SW
van Rensburg
Estrelita Janse
EJ
D016915:AIDS Vaccines / Q000235:genetics* / Q000276:immunology; D000818:Animals; D002460:Cell Line; D016384:Consensus Sequence / Q000276:immunology*; D005260:Female; D015754:Genes, nef / Q000235:genetics* / Q000276:immunology; D015757:Genes, rev / Q000235:genetics* / Q000276:immunology; D015756:Genes, tat / Q000235:genetics* / Q000276:immunology; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D019444:Vaccines, DNA / Q000145:classification / Q000235:genetics* / Q000276:immunology; D015164:Vaccines, Inactivated / Q000235:genetics / Q000276:immunology
D016915:AIDS Vaccines; D019444:Vaccines, DNA; D015164:Vaccines, Inactivated