title: The porcine circovirus type 1 capsid gene promoter improves antigen expression and immunogenicity in a HIV-1 plasmid vaccine.
abstract: BACKGROUND
  One of the promising avenues for development of vaccines against Human immunodeficiency virus type 1 (HIV-1) and other human pathogens is the use of plasmid-based DNA vaccines. However, relatively large doses of plasmid must be injected for a relatively weak response. We investigated whether genome elements from Porcine circovirus type 1 (PCV-1), an apathogenic small ssDNA-containing virus, had useful expression-enhancing properties that could allow dose-sparing in a plasmid vaccine.
  
  
  RESULTS
  The linearised PCV-1 genome inserted 5' of the CMV promoter in the well-characterised HIV-1 plasmid vaccine pTHgrttnC increased expression of the polyantigen up to 2-fold, and elicited 3-fold higher CTL responses in mice at 10-fold lower doses than unmodified pTHgrttnC. The PCV-1 capsid gene promoter (Pcap) alone was equally effective. Enhancing activity was traced to a putative composite host transcription factor binding site and a "Conserved Late Element" transcription-enhancing sequence previously unidentified in circoviruses.
  
  
  CONCLUSIONS
  We identified a novel PCV-1 genome-derived enhancer sequence that significantly increased antigen expression from plasmids in in vitro assays, and improved immunogenicity in mice of the HIV-1 subtype C vaccine plasmid, pTHgrttnC. This should allow significant dose sparing of, or increased responses to, this and other plasmid-based vaccines. We also report investigations of the potential of other circovirus-derived sequences to be similarly used.
authors.affiliation: Department of Molecular and Cell Biology, Faculty of Science, University of Cape Town, Rondebosch, Cape Town, 7701 South Africa.
authors.forename: Fiona L
authors.initials: FL
authors.lastname: Tanzer
authors.forename: Enid G
authors.initials: EG
authors.lastname: Shephard
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Palmer
authors.forename: Marieta
authors.initials: M
authors.lastname: Burger
authors.forename: Anna-Lise
authors.initials: AL
authors.lastname: Williamson
authors.forename: Edward P
authors.initials: EP
authors.lastname: Rybicki
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D036022:Capsid Proteins / Q000235:genetics*; D017925:Circovirus / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D016679:Genome, Viral; D057809:HEK293 Cells; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000956:Antigens, Viral; D036022:Capsid Proteins; D019444:Vaccines, DNA