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Title: Mechanisms of BCG-induced CD4 T cell-mediated immunity against mycobacterium bovis in the BALB/c mouse
Author: Kaveh , Daryan Alexander
ISNI:       0000 0004 5372 415X
Awarding Body: St George's, University of London
Current Institution: St George's, University of London
Date of Award: 2015
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The only available tuberculosis vaccine is BCG, but this requires urgent replacement or improvement for more efficacious use in the prevention of the large burden of disease in both humans and cattle. The protection provided by BCG remains valuable and in order to facilitate further vaccine development, the underlying protective mechanisms require understanding. In this thesis the putative role of the CD4 T cell response was examined. Collectively it was shown that BCG immunisation of BALB/c mice led to their colonisation by the live BCG vaccine bacilli. By six weeks postimmunisation the vaccination induced populations of antigen-specific CD4 T cells derived from the spleen and the lung which exhibited immediate effector cytokine functionality on antigen recognition. Further examinations of these cells indicated they putatively represented a canonical effector memory rather than central memory CD4 T cell population. The number of these BCG-induced antigen-specific CD4 T cells expanded on challenge infection with virulent Mycobacterium bovis, supporting their association with the protection afforded by the vaccine. In long-term vaccinates, the viable BCG bacilli continued to persist indefinitely, accompanied by the stability of both this putative effector memory CD4 T cell population and the protective capacity of the vaccine. However, elimination of the persistence of the vaccine bacilli, by antibiotic treatment, abrogated the detection of these CD4 T cells and reduced the protective capacity of the vaccine by around 50%, inferring both are dependent on live BCG persistence. The remaining independent mechanism of protection remains unclear. During this work, emphasis was also made on the potential influence and limitations of assay methodology used in analysing antigen -specific CD4 T cells. These results have important implications for our understanding of the potential mechanisms of BCG induced CD4 T cell-mediated immunity in the mouse model and its interpretation for use in vaccine development.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available