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HIV-1 strain-specific neutralizing antibody responses and the dynamics of viral evolution
It is widely held that for an HIV-1 vaccine to provide sterilizing immunity, it would need to elicit broadly neutralizing antibodies (bnAbs). However, factors underlying the development of these antibodies are not clear. There is evidence to suggest that in some individuals who develop bnAbs, the de...
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| Format: | Thesis |
| Language: | English |
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Department of Clinical Laboratory Sciences
2018
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| _version_ | 1867613977686573056 |
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| access_status_str | Open Access |
| author | Majara, Lerato Charlotte |
| author2 | Williamson, Carolyn |
| author_browse | Majara, Lerato Charlotte Williamson, Carolyn |
| author_facet | Williamson, Carolyn Majara, Lerato Charlotte |
| author_sort | Majara, Lerato Charlotte |
| collection | Thesis |
| description | It is widely held that for an HIV-1 vaccine to provide sterilizing immunity, it would need to elicit broadly neutralizing antibodies (bnAbs). However, factors underlying the development of these antibodies are not clear. There is evidence to suggest that in some individuals who develop bnAbs, the development of breadth is influenced by the co-evolution of the transmitted/founder (t/f) virus and earlier strain-specific neutralizing antibody (ssnAb) responses. Here we characterized the viral evolution, ssnAb and bnAbs responses in CAP292, an HIV-1 infected woman who developed bnAb responses from one year post infection. We used single genome amplification (SGA) to characterize viral evolution at four time points: at acute infection; after the development of strain-specific neutralizing responses; at the first detection of the broadly neutralizing antibody response; and lastly, at the peak of the broad response. We identified the t/f virus, and generated chimeric viruses from this to determine the targets of the ssnAb responses. A panel of site-directed mutant viruses were used to map the specificity of the bnAb responses. Our data indicated that infection was most likely founded by a single virus and that the first wave of ssnAbs emerged at 14 weeks post infection (w.p.i), targeting the V1V2 loop of Envelope (Env). A second wave of ssnAbs, possibly targeting the C3V4 region, emerged by 30 w.p.i. Two distinct viral clusters were detected by the time the bnAb response peaked, suggesting the presence of distinct escape pathways. Mapping of the bnAb specificities indicated that CAP292 produced PGT128-like bnAb responses targeted toward the 332 glycan. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/28263 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| last_indexed | 2026-06-10T12:44:43.480Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2018 |
| publishDateRange | 2018 |
| publishDateSort | 2018 |
| publisher | Department of Clinical Laboratory Sciences |
| publisherStr | Department of Clinical Laboratory Sciences |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/28263 HIV-1 strain-specific neutralizing antibody responses and the dynamics of viral evolution Majara, Lerato Charlotte Williamson, Carolyn Anthony, Colin Scott Pathology It is widely held that for an HIV-1 vaccine to provide sterilizing immunity, it would need to elicit broadly neutralizing antibodies (bnAbs). However, factors underlying the development of these antibodies are not clear. There is evidence to suggest that in some individuals who develop bnAbs, the development of breadth is influenced by the co-evolution of the transmitted/founder (t/f) virus and earlier strain-specific neutralizing antibody (ssnAb) responses. Here we characterized the viral evolution, ssnAb and bnAbs responses in CAP292, an HIV-1 infected woman who developed bnAb responses from one year post infection. We used single genome amplification (SGA) to characterize viral evolution at four time points: at acute infection; after the development of strain-specific neutralizing responses; at the first detection of the broadly neutralizing antibody response; and lastly, at the peak of the broad response. We identified the t/f virus, and generated chimeric viruses from this to determine the targets of the ssnAb responses. A panel of site-directed mutant viruses were used to map the specificity of the bnAb responses. Our data indicated that infection was most likely founded by a single virus and that the first wave of ssnAbs emerged at 14 weeks post infection (w.p.i), targeting the V1V2 loop of Envelope (Env). A second wave of ssnAbs, possibly targeting the C3V4 region, emerged by 30 w.p.i. Two distinct viral clusters were detected by the time the bnAb response peaked, suggesting the presence of distinct escape pathways. Mapping of the bnAb specificities indicated that CAP292 produced PGT128-like bnAb responses targeted toward the 332 glycan. 2018-06-22T07:27:44Z 2018-06-22T07:27:44Z 2016 Master Thesis Masters MSc (Med) http://hdl.handle.net/11427/28263 eng application/pdf Department of Clinical Laboratory Sciences Faculty of Health Sciences University of Cape Town |
| spellingShingle | Pathology Majara, Lerato Charlotte HIV-1 strain-specific neutralizing antibody responses and the dynamics of viral evolution |
| thesis_degree_str | Master's |
| title | HIV-1 strain-specific neutralizing antibody responses and the dynamics of viral evolution |
| title_full | HIV-1 strain-specific neutralizing antibody responses and the dynamics of viral evolution |
| title_fullStr | HIV-1 strain-specific neutralizing antibody responses and the dynamics of viral evolution |
| title_full_unstemmed | HIV-1 strain-specific neutralizing antibody responses and the dynamics of viral evolution |
| title_short | HIV-1 strain-specific neutralizing antibody responses and the dynamics of viral evolution |
| title_sort | hiv 1 strain specific neutralizing antibody responses and the dynamics of viral evolution |
| topic | Pathology |
| url | http://hdl.handle.net/11427/28263 |
| work_keys_str_mv | AT majaraleratocharlotte hiv1strainspecificneutralizingantibodyresponsesandthedynamicsofviralevolution |