BCG-specific T cell proliferation and cytotoxic capacity in infants as risk of tuberculosis disease, following newborn BCG vaccination

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dc.contributor.advisorHanekom, Willem Aen_ZA
dc.contributor.advisorScriba, Thomasen_ZA
dc.contributor.authorKeyser, Alanaen_ZA
dc.date.accessioned2015-09-25T07:34:26Z
dc.date.available2015-09-25T07:34:26Z
dc.date.issued2014en_ZA
dc.descriptionIncludes bibliographical references.en_ZA
dc.description.abstractBCG is the only vaccine against tuberculosis and has been used for over 90 years. BCG efficacy is variable, especially in countries with high TB prevalence, where over a million deaths due to tuberculosis, are still reported annually. New TB vaccines are under development to either replace or boost the BCG vaccine. However, our understanding of the immune response required for protection against TB disease, remains inadequate. Identification of a protective immune response is only possible in a clinical trial of an efficacious vaccine, allowing comparison of vaccine-induced immune responses in protected and unprotected individuals. In the absence of such a vaccine, as is the case with TB, we can only explore biomarkers of risk of disease. The most commonly measured outcomes of anti-mycobacterial immunity in clinical trials, specific Th1 cells, are typically thought to be protective in TB. However, to date, human mycobacteria-specific Th1 responses have not correlated with risk of TB disease. New approaches are urgently required to identify other factors at play in conferring protection against TB. In this thesis, we explored BCG-specific cytotoxic T cells as candidate correlates of risk of TB disease in BCG-vaccinated infants. We hypothesized that reduced production of cytotoxic molecules by T cells in response to BCG are associated with risk of developing TB disease. We designed a case/control study nested within a large trial of newborn BCG-vaccination.Blood was collected at 10 weeks and infants, were followed up for two years.We compared outcomes in infants ultimately diagnosed with TB (at risk of TB disease) and two groups of healthy infants (not at risk of TB disease), the first group had household contact with TB cases, the second group were randomly selected from the community, which is endemic for TB. Amongst these groups, we designated a training and a test cohort to allow validation of candidate correlates of risk of TB.en_ZA
dc.identifier.apacitationKeyser, A. (2014). <i>BCG-specific T cell proliferation and cytotoxic capacity in infants as risk of tuberculosis disease, following newborn BCG vaccination</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Department of Paediatrics and Child Health. Retrieved from http://hdl.handle.net/11427/14085en_ZA
dc.identifier.chicagocitationKeyser, Alana. <i>"BCG-specific T cell proliferation and cytotoxic capacity in infants as risk of tuberculosis disease, following newborn BCG vaccination."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Department of Paediatrics and Child Health, 2014. http://hdl.handle.net/11427/14085en_ZA
dc.identifier.citationKeyser, A. 2014. BCG-specific T cell proliferation and cytotoxic capacity in infants as risk of tuberculosis disease, following newborn BCG vaccination. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Keyser, Alana AB - BCG is the only vaccine against tuberculosis and has been used for over 90 years. BCG efficacy is variable, especially in countries with high TB prevalence, where over a million deaths due to tuberculosis, are still reported annually. New TB vaccines are under development to either replace or boost the BCG vaccine. However, our understanding of the immune response required for protection against TB disease, remains inadequate. Identification of a protective immune response is only possible in a clinical trial of an efficacious vaccine, allowing comparison of vaccine-induced immune responses in protected and unprotected individuals. In the absence of such a vaccine, as is the case with TB, we can only explore biomarkers of risk of disease. The most commonly measured outcomes of anti-mycobacterial immunity in clinical trials, specific Th1 cells, are typically thought to be protective in TB. However, to date, human mycobacteria-specific Th1 responses have not correlated with risk of TB disease. New approaches are urgently required to identify other factors at play in conferring protection against TB. In this thesis, we explored BCG-specific cytotoxic T cells as candidate correlates of risk of TB disease in BCG-vaccinated infants. We hypothesized that reduced production of cytotoxic molecules by T cells in response to BCG are associated with risk of developing TB disease. We designed a case/control study nested within a large trial of newborn BCG-vaccination.Blood was collected at 10 weeks and infants, were followed up for two years.We compared outcomes in infants ultimately diagnosed with TB (at risk of TB disease) and two groups of healthy infants (not at risk of TB disease), the first group had household contact with TB cases, the second group were randomly selected from the community, which is endemic for TB. Amongst these groups, we designated a training and a test cohort to allow validation of candidate correlates of risk of TB. DA - 2014 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2014 T1 - BCG-specific T cell proliferation and cytotoxic capacity in infants as risk of tuberculosis disease, following newborn BCG vaccination TI - BCG-specific T cell proliferation and cytotoxic capacity in infants as risk of tuberculosis disease, following newborn BCG vaccination UR - http://hdl.handle.net/11427/14085 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/14085
dc.identifier.vancouvercitationKeyser A. BCG-specific T cell proliferation and cytotoxic capacity in infants as risk of tuberculosis disease, following newborn BCG vaccination. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Department of Paediatrics and Child Health, 2014 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/14085en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentDepartment of Paediatrics and Child Healthen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherChild and Adolescent Healthen_ZA
dc.titleBCG-specific T cell proliferation and cytotoxic capacity in infants as risk of tuberculosis disease, following newborn BCG vaccinationen_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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