HIV-1 strain-specific neutralizing antibody responses and the dynamics of viral evolution

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dc.contributor.advisorWilliamson, Carolynen_ZA
dc.contributor.advisorAnthony, Colin Scotten_ZA
dc.contributor.authorMajara, Lerato Charlotteen_ZA
dc.date.accessioned2018-06-22T07:27:44Z
dc.date.available2018-06-22T07:27:44Z
dc.date.issued2016en_ZA
dc.description.abstractIt 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.en_ZA
dc.identifier.apacitationMajara, L. C. (2016). <i>HIV-1 strain-specific neutralizing antibody responses and the dynamics of viral evolution</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences. Retrieved from http://hdl.handle.net/11427/28263en_ZA
dc.identifier.chicagocitationMajara, Lerato Charlotte. <i>"HIV-1 strain-specific neutralizing antibody responses and the dynamics of viral evolution."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences, 2016. http://hdl.handle.net/11427/28263en_ZA
dc.identifier.citationMajara, L. 2016. HIV-1 strain-specific neutralizing antibody responses and the dynamics of viral evolution. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Majara, Lerato Charlotte AB - 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. DA - 2016 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2016 T1 - HIV-1 strain-specific neutralizing antibody responses and the dynamics of viral evolution TI - HIV-1 strain-specific neutralizing antibody responses and the dynamics of viral evolution UR - http://hdl.handle.net/11427/28263 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/28263
dc.identifier.vancouvercitationMajara LC. HIV-1 strain-specific neutralizing antibody responses and the dynamics of viral evolution. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences, 2016 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/28263en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentDepartment of Clinical Laboratory Sciencesen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherPathologyen_ZA
dc.titleHIV-1 strain-specific neutralizing antibody responses and the dynamics of viral evolutionen_ZA
dc.typeMaster Thesis
dc.type.qualificationlevelMasters
dc.type.qualificationnameMSc (Med)en_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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