Development of novel T cell assays and assessment of immune recognition to latency associated M.tuberculosis-specific antigens Rv2660 and Rv2659

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dc.contributor.advisorHanekom, Willem Aen_ZA
dc.contributor.advisorAbel, Brianen_ZA
dc.contributor.authorGovender, Lerisaen_ZA
dc.date.accessioned2014-07-28T14:57:24Z
dc.date.available2014-07-28T14:57:24Z
dc.date.issued2010en_ZA
dc.descriptionIncludes abstract.
dc.descriptionIncludes bibliographical references (leaves 93-109).
dc.description.abstractNearly 130 years have elapsed since the discovery of Mycobacterium tuberculosis (M.tb), the causative agent of tuberculosis, yet today it is estimated that 1 in every 3 of the worldʼs population is infected with this pathogen. In South Africa alone there were approximately 1000 new TB cases per 100 000 population in 2007, ranking the country second in incidence rate, globally. Hence research into new vaccine strategies to control the epidemic is vital. Current vaccines under development are prophylactic and designed to boost pre-existing immunity induced by the only licensed TB vaccine, BCG. A new approach is the development of a post-infection vaccine aimed at inducing an immune response that prevents progression to TB disease when administered to individuals latently infected with M.tb. This vaccine would have a dramatic impact on the worldwide TB burden. Our objective was to address 2 areas in TB vaccinology, firstly a novel postinfection TB vaccine strategy, and secondly, optimal measurement of vaccineinduced responses using a new immunological assay. The aim of the first study was to investigate human T cell responses to antigens that have been associated with M.tb latency. Rv2660 and Rv2659 were investigated, as these antigens are candidate antigens for a postinfection vaccine based on findings from in vitro models of M.tb suggesting preferential expression during latency in vivo. No information exists on the immune response to these antigens in M.tb infected or TB diseased individuals. Hence, we investigated the immune recognition of Rv2660 and Rv2659 in these 2 groups, and further characterised the nature of these antigen-specific T cell responses. We observed that (i) these antigens are significantly more likely to be recognised during M.tb infection compared with TB disease as shown by measurement of soluble IFN-γ in response to the specific antigens, (ii) M.tb infected persons had greater Rv2660- and Rv2659- specific CD4+ T cell proliferation and associated cytokine expression compared, with TB diseased persons. We propose that Rv2660 and Rv2659 may be candidates for incorporation into a post-infection vaccine.en_ZA
dc.identifier.apacitationGovender, L. (2010). <i>Development of novel T cell assays and assessment of immune recognition to latency associated M.tuberculosis-specific antigens Rv2660 and Rv2659</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences. Retrieved from http://hdl.handle.net/11427/3163en_ZA
dc.identifier.chicagocitationGovender, Lerisa. <i>"Development of novel T cell assays and assessment of immune recognition to latency associated M.tuberculosis-specific antigens Rv2660 and Rv2659."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences, 2010. http://hdl.handle.net/11427/3163en_ZA
dc.identifier.citationGovender, L. 2010. Development of novel T cell assays and assessment of immune recognition to latency associated M.tuberculosis-specific antigens Rv2660 and Rv2659. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Govender, Lerisa AB - Nearly 130 years have elapsed since the discovery of Mycobacterium tuberculosis (M.tb), the causative agent of tuberculosis, yet today it is estimated that 1 in every 3 of the worldʼs population is infected with this pathogen. In South Africa alone there were approximately 1000 new TB cases per 100 000 population in 2007, ranking the country second in incidence rate, globally. Hence research into new vaccine strategies to control the epidemic is vital. Current vaccines under development are prophylactic and designed to boost pre-existing immunity induced by the only licensed TB vaccine, BCG. A new approach is the development of a post-infection vaccine aimed at inducing an immune response that prevents progression to TB disease when administered to individuals latently infected with M.tb. This vaccine would have a dramatic impact on the worldwide TB burden. Our objective was to address 2 areas in TB vaccinology, firstly a novel postinfection TB vaccine strategy, and secondly, optimal measurement of vaccineinduced responses using a new immunological assay. The aim of the first study was to investigate human T cell responses to antigens that have been associated with M.tb latency. Rv2660 and Rv2659 were investigated, as these antigens are candidate antigens for a postinfection vaccine based on findings from in vitro models of M.tb suggesting preferential expression during latency in vivo. No information exists on the immune response to these antigens in M.tb infected or TB diseased individuals. Hence, we investigated the immune recognition of Rv2660 and Rv2659 in these 2 groups, and further characterised the nature of these antigen-specific T cell responses. We observed that (i) these antigens are significantly more likely to be recognised during M.tb infection compared with TB disease as shown by measurement of soluble IFN-γ in response to the specific antigens, (ii) M.tb infected persons had greater Rv2660- and Rv2659- specific CD4+ T cell proliferation and associated cytokine expression compared, with TB diseased persons. We propose that Rv2660 and Rv2659 may be candidates for incorporation into a post-infection vaccine. DA - 2010 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2010 T1 - Development of novel T cell assays and assessment of immune recognition to latency associated M.tuberculosis-specific antigens Rv2660 and Rv2659 TI - Development of novel T cell assays and assessment of immune recognition to latency associated M.tuberculosis-specific antigens Rv2660 and Rv2659 UR - http://hdl.handle.net/11427/3163 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/3163
dc.identifier.vancouvercitationGovender L. Development of novel T cell assays and assessment of immune recognition to latency associated M.tuberculosis-specific antigens Rv2660 and Rv2659. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences, 2010 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/3163en_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.otherClinical Laboratory Sciencesen_ZA
dc.titleDevelopment of novel T cell assays and assessment of immune recognition to latency associated M.tuberculosis-specific antigens Rv2660 and Rv2659en_ZA
dc.typeMaster Thesis
dc.type.qualificationlevelMasters
dc.type.qualificationnameMScen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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