Construction and evaluation of three candidate vaccines expressing HIV-1 subtype-C mosaic Gag

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dc.contributor.advisorChapman, Rosen_ZA
dc.contributor.advisorWilliamson, Anna-Liseen_ZA
dc.contributor.advisorDouglass, Nikien_ZA
dc.contributor.advisorChege, Geralden_ZA
dc.contributor.authorJongwe, Tsungai Ivaien_ZA
dc.date.accessioned2016-03-03T14:46:04Z
dc.date.available2016-03-03T14:46:04Z
dc.date.issued2015en_ZA
dc.descriptionIncludes bibliographical referencesen_ZA
dc.description.abstractOf the 35 million people living with HIV-1 globally, approximately 71.4% are in the resource-limited sub-Saharan Africa. The immense sequence diversity of HIV-1, even within subtypes, makes it challenging to develop effective vaccines that target a wide range of HIV subtypes. Mosaic immunogens have been computationally designed to specifically overcome this hurdle by maximizing the inclusion of common T cell epitopes. When compared to consensus immunogens, polyvalent mosaic immunogens of HIV-1 group M have shown increased breadth and depth of antigen-specific T-cell responses. More than 90% of HIV positive individuals in sub-Saharan Africa are infected with HIV-1 subtype C (HIV-1C). We therefore designed, constructed, and evaluated candidate vaccines expressing HIV-1C mosaic Gag (GagM) in a proof of concept study. Gag was chosen as the most appropriate target for a T cell-based vaccine as there are many studies correlating control of HIV viral load with T cell responses to Gag. The immunogen was designed by Fischer et al., 2007 (1). Three different vaccine platforms were chosen based on their different strengths to be used in prime-boost regimens to determine the immunogenicity of HIV-1C GagM in mice. The first was a pantothenic auxotroph of the tuberculosis vaccine Mycobacterium bovis Bacille Calmette Guérin (BCG). The second was a DNA vaccine vector with enhanced expression of transgenes due to a novel enhancer element from porcine circovirus type 1, which has been demonstrated to increase gene expression. The third vaccine vector selected was the well characterised poxvirus modified vaccinia Ankara (MVA).en_ZA
dc.identifier.apacitationJongwe, T. I. (2015). <i>Construction and evaluation of three candidate vaccines expressing HIV-1 subtype-C mosaic Gag</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Division of Medical Biochemistry. Retrieved from http://hdl.handle.net/11427/17428en_ZA
dc.identifier.chicagocitationJongwe, Tsungai Ivai. <i>"Construction and evaluation of three candidate vaccines expressing HIV-1 subtype-C mosaic Gag."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Division of Medical Biochemistry, 2015. http://hdl.handle.net/11427/17428en_ZA
dc.identifier.citationJongwe, T. 2015. Construction and evaluation of three candidate vaccines expressing HIV-1 subtype-C mosaic Gag. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Jongwe, Tsungai Ivai AB - Of the 35 million people living with HIV-1 globally, approximately 71.4% are in the resource-limited sub-Saharan Africa. The immense sequence diversity of HIV-1, even within subtypes, makes it challenging to develop effective vaccines that target a wide range of HIV subtypes. Mosaic immunogens have been computationally designed to specifically overcome this hurdle by maximizing the inclusion of common T cell epitopes. When compared to consensus immunogens, polyvalent mosaic immunogens of HIV-1 group M have shown increased breadth and depth of antigen-specific T-cell responses. More than 90% of HIV positive individuals in sub-Saharan Africa are infected with HIV-1 subtype C (HIV-1C). We therefore designed, constructed, and evaluated candidate vaccines expressing HIV-1C mosaic Gag (GagM) in a proof of concept study. Gag was chosen as the most appropriate target for a T cell-based vaccine as there are many studies correlating control of HIV viral load with T cell responses to Gag. The immunogen was designed by Fischer et al., 2007 (1). Three different vaccine platforms were chosen based on their different strengths to be used in prime-boost regimens to determine the immunogenicity of HIV-1C GagM in mice. The first was a pantothenic auxotroph of the tuberculosis vaccine Mycobacterium bovis Bacille Calmette Guérin (BCG). The second was a DNA vaccine vector with enhanced expression of transgenes due to a novel enhancer element from porcine circovirus type 1, which has been demonstrated to increase gene expression. The third vaccine vector selected was the well characterised poxvirus modified vaccinia Ankara (MVA). DA - 2015 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2015 T1 - Construction and evaluation of three candidate vaccines expressing HIV-1 subtype-C mosaic Gag TI - Construction and evaluation of three candidate vaccines expressing HIV-1 subtype-C mosaic Gag UR - http://hdl.handle.net/11427/17428 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/17428
dc.identifier.vancouvercitationJongwe TI. Construction and evaluation of three candidate vaccines expressing HIV-1 subtype-C mosaic Gag. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Division of Medical Biochemistry, 2015 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/17428en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentDivision of Medical Biochemistryen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherMedical Microbiologyen_ZA
dc.titleConstruction and evaluation of three candidate vaccines expressing HIV-1 subtype-C mosaic Gagen_ZA
dc.typeDoctoral Thesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationnamePhDen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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