Includes bibliographical references / 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).
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:uct/oai:localhost:11427/17428 |
| Date | January 2015 |
| Creators | Jongwe, Tsungai Ivai |
| Contributors | Chapman, Ros, Williamson, Anna-Lise, Douglass, Niki, Chege, Gerald |
| Publisher | University of Cape Town, Faculty of Health Sciences, Division of Medical Biochemistry |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Doctoral Thesis, Doctoral, PhD |
| Format | application/pdf |
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