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Systems analysis of the CD4 T cell response induced by the novel subunit tuberculosis vaccine, H1:IC31
Includes bibliographical references
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| Main Author: | |
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| Other Authors: | |
| Format: | Thesis |
| Language: | English |
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Department of Paediatrics and Child Health
2016
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| _version_ | 1867613214130307072 |
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| access_status_str | Open Access |
| author | Musvosvi, Munyaradzi Nyasha |
| author2 | Scriba, Thomas J |
| author_browse | Musvosvi, Munyaradzi Nyasha Scriba, Thomas J |
| author_facet | Scriba, Thomas J Musvosvi, Munyaradzi Nyasha |
| author_sort | Musvosvi, Munyaradzi Nyasha |
| collection | Thesis |
| description | Includes bibliographical references |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/16724 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| last_indexed | 2026-06-10T12:32:34.479Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2016 |
| publishDateRange | 2016 |
| publishDateSort | 2016 |
| publisher | Department of Paediatrics and Child Health |
| publisherStr | Department of Paediatrics and Child Health |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/16724 Systems analysis of the CD4 T cell response induced by the novel subunit tuberculosis vaccine, H1:IC31 Musvosvi, Munyaradzi Nyasha Scriba, Thomas J Penn-Nicholson, Adam Paediatrics and Child Health Includes bibliographical references In this study we sought to more comprehensively analyse antigen-specific CD4 T cell responses induced by vaccination and to examine the effects of latent M. tb infection on these responses. We had two broad objectives: Firstly, to determine the effects of latent M. tb infection on epitope recognition by mycobacteria-specific CD4 T cells and to design HLA class II tetramers for detection of these cells. Secondly, to characterise antigen-specific CD4 T cells following vaccination with the novel vaccine candidate, H1:IC31, by measuring transcriptomic, phenotypic and functional attributes, and to determine the effects of latent infection on these responses. Firstly, we found that acquisition of M.tb infection did not alter the breadth and/or pattern of Ag85A/ B CD4 T cell epitopes recognised. We determined the HLA allele restriction of identified epitopes, and designed HLA class II tetramers for detection of Ag85-specific CD4 T cells. These results suggest that latent infection does not alter CD4 T cell epitope breadth within Ag85A/ B elicited by BCG vaccination and/or exposure to environmental mycobacteria. The second finding of this work is that underlying infection drives a more effector-like H1-specific CD4 T response after vaccination. Following vaccination M. tb-infected adolescents had higher frequencies of H1-specific CD4 T cells compared with uninfected adolescents. Additionally, H1-specific CD4 T cells from infected adolescents predominantly displayed a CCR7 - CD45RA - effector memory phenotype, had higher proportions of IFN-γ + TNF-α + IL-2 + cells, and expressed higher levels mRNA transcripts encoding effector molecules such as granzyme K and perforin, compared with uninfected adolescents. By contrast, H1-specific CD4 T cells in uninfected adolescents displayed a less differentiated memory phenotype, and had increased expression of central memory genes, compared to cells from infected adolescents. Thirdly, we found that Ag85B and ESAT-6-specific CD4 T cells exhibited markedly distinct transcriptomic profiles, memory phenotypes and cytokine expression patterns in M.tb infected adolescents. The data suggested that ESAT-6-specific cells preferentially drove the effector-like H1-specific response in M.tb infected adolescents. We conclude that while underlying M.tb infection does not affect the epitopes recognized by mycobacteria-specific CD4 T cells, but may promote and maintain effector memory antigen-specific CD4 T cells endowed with immediate effector function and tissue homing. 2016-02-03T14:29:28Z 2016-02-03T14:29:28Z 2015 Doctoral Thesis Doctoral PhD http://hdl.handle.net/11427/16724 eng application/pdf Department of Paediatrics and Child Health Faculty of Health Sciences University of Cape Town |
| spellingShingle | Paediatrics and Child Health Musvosvi, Munyaradzi Nyasha Systems analysis of the CD4 T cell response induced by the novel subunit tuberculosis vaccine, H1:IC31 |
| thesis_degree_str | Doctoral |
| title | Systems analysis of the CD4 T cell response induced by the novel subunit tuberculosis vaccine, H1:IC31 |
| title_full | Systems analysis of the CD4 T cell response induced by the novel subunit tuberculosis vaccine, H1:IC31 |
| title_fullStr | Systems analysis of the CD4 T cell response induced by the novel subunit tuberculosis vaccine, H1:IC31 |
| title_full_unstemmed | Systems analysis of the CD4 T cell response induced by the novel subunit tuberculosis vaccine, H1:IC31 |
| title_short | Systems analysis of the CD4 T cell response induced by the novel subunit tuberculosis vaccine, H1:IC31 |
| title_sort | systems analysis of the cd4 t cell response induced by the novel subunit tuberculosis vaccine h1 ic31 |
| topic | Paediatrics and Child Health |
| url | http://hdl.handle.net/11427/16724 |
| work_keys_str_mv | AT musvosvimunyaradzinyasha systemsanalysisofthecd4tcellresponseinducedbythenovelsubunittuberculosisvaccineh1ic31 |