Priming with a recombinant pantothenate auxotroph of Mycobacterium bovis BCG and boosting with MVA elicits HIV-1 Gag specific CD8+ T cells

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dc.contributor.authorChapman, Rosamunden_ZA
dc.contributor.authorShephard, Eniden_ZA
dc.contributor.authorStutz, Helenen_ZA
dc.contributor.authorDouglass, Nicolaen_ZA
dc.contributor.authorSambandamurthy, Vasanen_ZA
dc.contributor.authorGarcia, Ireneen_ZA
dc.contributor.authorRyffel, Bernharden_ZA
dc.contributor.authorJacobs, Williamen_ZA
dc.contributor.authorWilliamson, Anna-Liseen_ZA
dc.date.accessioned2016-01-11T06:53:34Z
dc.date.available2016-01-11T06:53:34Z
dc.date.issued2012en_ZA
dc.description.abstractA safe and effective HIV vaccine is required to significantly reduce the number of people becoming infected with HIV each year. In this study wild type Mycobacterium bovis BCG Pasteur and an attenuated pantothenate auxotroph strain (BCGΔ panCD ) that is safe in SCID mice, have been compared as vaccine vectors for HIV-1 subtype C Gag. Genetically stable vaccines BCG[pHS400] (BCG-Gag) and BCGΔ panCD [pHS400] (BCGpan-Gag) were generated using the Pasteur strain of BCG, and a panothenate auxotroph of Pasteur respectively. Stability was achieved by the use of a codon optimised gag gene and deletion of the hsp60-lysA promoter-gene cassette from the episomal vector pCB119. In this vector expression of gag is driven by the mtrA promoter and the Gag protein is fused to the Mycobacterium tuberculosis 19 kDa signal sequence. Both BCG-Gag and BCGpan-Gag primed the immune system of BALB/c mice for a boost with a recombinant modified vaccinia virus Ankara expressing Gag (MVA-Gag). After the boost high frequencies of predominantly Gag-specific CD8 + T cells were detected when BCGpan-Gag was the prime in contrast to induction of predominantly Gag-specific CD4 + T cells when priming with BCG-Gag. The differing Gag-specific T-cell phenotype elicited by the prime-boost regimens may be related to the reduced inflammation observed with the pantothenate auxotroph strain compared to the parent strain. These features make BCGpan-Gag a more desirable HIV vaccine candidate than BCG-Gag. Although no Gag-specific cells could be detected after vaccination of BALB/c mice with either recombinant BCG vaccine alone, BCGpan-Gag protected mice against a surrogate vaccinia virus challenge.en_ZA
dc.identifier.apacitationChapman, R., Shephard, E., Stutz, H., Douglass, N., Sambandamurthy, V., Garcia, I., ... Williamson, A. (2012). Priming with a recombinant pantothenate auxotroph of Mycobacterium bovis BCG and boosting with MVA elicits HIV-1 Gag specific CD8+ T cells. <i>PLoS One</i>, http://hdl.handle.net/11427/16285en_ZA
dc.identifier.chicagocitationChapman, Rosamund, Enid Shephard, Helen Stutz, Nicola Douglass, Vasan Sambandamurthy, Irene Garcia, Bernhard Ryffel, William Jacobs, and Anna-Lise Williamson "Priming with a recombinant pantothenate auxotroph of Mycobacterium bovis BCG and boosting with MVA elicits HIV-1 Gag specific CD8+ T cells." <i>PLoS One</i> (2012) http://hdl.handle.net/11427/16285en_ZA
dc.identifier.citationChapman, R., Shephard, E., Stutz, H., Douglass, N., Sambandamurthy, V., Garcia, I., ... & Williamson, A. L. (2012). Priming with a recombinant pantothenate auxotroph of Mycobacterium bovis BCG and boosting with MVA elicits HIV-1 Gag specific CD8 () T cells. PLoS One, 7, e32769. doi:10.1371/journal.pone.0032769en_ZA
dc.identifier.ris TY - Journal Article AU - Chapman, Rosamund AU - Shephard, Enid AU - Stutz, Helen AU - Douglass, Nicola AU - Sambandamurthy, Vasan AU - Garcia, Irene AU - Ryffel, Bernhard AU - Jacobs, William AU - Williamson, Anna-Lise AB - A safe and effective HIV vaccine is required to significantly reduce the number of people becoming infected with HIV each year. In this study wild type Mycobacterium bovis BCG Pasteur and an attenuated pantothenate auxotroph strain (BCGΔ panCD ) that is safe in SCID mice, have been compared as vaccine vectors for HIV-1 subtype C Gag. Genetically stable vaccines BCG[pHS400] (BCG-Gag) and BCGΔ panCD [pHS400] (BCGpan-Gag) were generated using the Pasteur strain of BCG, and a panothenate auxotroph of Pasteur respectively. Stability was achieved by the use of a codon optimised gag gene and deletion of the hsp60-lysA promoter-gene cassette from the episomal vector pCB119. In this vector expression of gag is driven by the mtrA promoter and the Gag protein is fused to the Mycobacterium tuberculosis 19 kDa signal sequence. Both BCG-Gag and BCGpan-Gag primed the immune system of BALB/c mice for a boost with a recombinant modified vaccinia virus Ankara expressing Gag (MVA-Gag). After the boost high frequencies of predominantly Gag-specific CD8 + T cells were detected when BCGpan-Gag was the prime in contrast to induction of predominantly Gag-specific CD4 + T cells when priming with BCG-Gag. The differing Gag-specific T-cell phenotype elicited by the prime-boost regimens may be related to the reduced inflammation observed with the pantothenate auxotroph strain compared to the parent strain. These features make BCGpan-Gag a more desirable HIV vaccine candidate than BCG-Gag. Although no Gag-specific cells could be detected after vaccination of BALB/c mice with either recombinant BCG vaccine alone, BCGpan-Gag protected mice against a surrogate vaccinia virus challenge. DA - 2012 DB - OpenUCT DO - 10.1371/journal.pone.0032769 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2012 T1 - Priming with a recombinant pantothenate auxotroph of Mycobacterium bovis BCG and boosting with MVA elicits HIV-1 Gag specific CD8+ T cells TI - Priming with a recombinant pantothenate auxotroph of Mycobacterium bovis BCG and boosting with MVA elicits HIV-1 Gag specific CD8+ T cells UR - http://hdl.handle.net/11427/16285 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16285
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0032769
dc.identifier.vancouvercitationChapman R, Shephard E, Stutz H, Douglass N, Sambandamurthy V, Garcia I, et al. Priming with a recombinant pantothenate auxotroph of Mycobacterium bovis BCG and boosting with MVA elicits HIV-1 Gag specific CD8+ T cells. PLoS One. 2012; http://hdl.handle.net/11427/16285.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2012 Chapman et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherVaccinesen_ZA
dc.subject.otherVaccination and immunizationen_ZA
dc.subject.otherHIV vaccinesen_ZA
dc.subject.otherPlasmid constructionen_ZA
dc.subject.otherMycobacterium tuberculosisen_ZA
dc.subject.otherRecombinant vaccinesen_ZA
dc.subject.otherImmune responseen_ZA
dc.subject.otherCytotoxic T cellsen_ZA
dc.titlePriming with a recombinant pantothenate auxotroph of Mycobacterium bovis BCG and boosting with MVA elicits HIV-1 Gag specific CD8+ T cellsen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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