The porcine circovirus type 1 capsid gene promoter improves antigen expression and immunogenicity in a HIV-1 plasmid vaccine

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dc.contributor.authorTanzer, Fionaen_ZA
dc.contributor.authorShephard, Eniden_ZA
dc.contributor.authorPalmer, Kennethen_ZA
dc.contributor.authorBurger, Marietaen_ZA
dc.contributor.authorWilliamson, Anna-Liseen_ZA
dc.contributor.authorRybicki, Edwarden_ZA
dc.date.accessioned2015-10-28T07:03:46Z
dc.date.available2015-10-28T07:03:46Z
dc.date.issued2011en_ZA
dc.description.abstractBACKGROUND: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.en_ZA
dc.identifier.apacitationTanzer, F., Shephard, E., Palmer, K., Burger, M., Williamson, A., & Rybicki, E. (2011). The porcine circovirus type 1 capsid gene promoter improves antigen expression and immunogenicity in a HIV-1 plasmid vaccine. <i>Virology Journal</i>, http://hdl.handle.net/11427/14467en_ZA
dc.identifier.chicagocitationTanzer, Fiona, Enid Shephard, Kenneth Palmer, Marieta Burger, Anna-Lise Williamson, and Edward Rybicki "The porcine circovirus type 1 capsid gene promoter improves antigen expression and immunogenicity in a HIV-1 plasmid vaccine." <i>Virology Journal</i> (2011) http://hdl.handle.net/11427/14467en_ZA
dc.identifier.citationTanzer, F. L., Shephard, E. G., Palmer, K. E., Burger, M., Williamson, A. L., & Rybicki, E. P. (2011). The porcine circovirus type 1 capsid gene promoter improves antigen expression and immunogenicity in a HIV-1 plasmid vaccine. Virol J, 8(1), 51.en_ZA
dc.identifier.ris TY - Journal Article AU - Tanzer, Fiona AU - Shephard, Enid AU - Palmer, Kenneth AU - Burger, Marieta AU - Williamson, Anna-Lise AU - Rybicki, Edward AB - 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. DA - 2011 DB - OpenUCT DO - 10.1186/1743-422X-8-51 DP - University of Cape Town J1 - Virology Journal LK - https://open.uct.ac.za PB - University of Cape Town PY - 2011 T1 - The porcine circovirus type 1 capsid gene promoter improves antigen expression and immunogenicity in a HIV-1 plasmid vaccine TI - The porcine circovirus type 1 capsid gene promoter improves antigen expression and immunogenicity in a HIV-1 plasmid vaccine UR - http://hdl.handle.net/11427/14467 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/14467
dc.identifier.urihttp://dx.doi.org/10.1186/1743-422X-8-51
dc.identifier.vancouvercitationTanzer F, Shephard E, Palmer K, Burger M, Williamson A, Rybicki E. The porcine circovirus type 1 capsid gene promoter improves antigen expression and immunogenicity in a HIV-1 plasmid vaccine. Virology Journal. 2011; http://hdl.handle.net/11427/14467.en_ZA
dc.language.isoengen_ZA
dc.publisherBioMed Central Ltden_ZA
dc.publisher.departmentDepartment of Molecular and Cell Biologyen_ZA
dc.publisher.facultyFaculty of Scienceen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution Licenseen_ZA
dc.rights.holder2011 Tanzer et al; licensee BioMed Central Ltd.en_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en_ZA
dc.sourceVirology Journalen_ZA
dc.source.urihttp://www.virologyj.com/en_ZA
dc.subject.otherBeak and feather disease virusen_ZA
dc.subject.otherPlasmid-based DNA vaccinesen_ZA
dc.titleThe porcine circovirus type 1 capsid gene promoter improves antigen expression and immunogenicity in a HIV-1 plasmid vaccineen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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