Characterisation of the T cell responses induced by BCG in infants over the first year of life

Master Thesis


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University of Cape Town

Mycobacterium bovis Bacille Calmette Guerin (BCG) is the only licensed tuberculosis (TB) vaccine. Despite the immunisation of 3 billion individuals with this vaccine, TB remains a major cause of mortality worldwide. Therefore, there is an urgent need for more effective TB vaccines. BCG is likely to remain central to future TB prevention strategies, which could include a BCG prime at birth, followed by boosts with novel TB vaccines within the first year of life, or at later ages. Therefore, a comprehensive understanding of BCG induced immunity is required for the successful design and implementation of novel TB vaccination strategies. This was addressed in the following two studies.The aim of the first study was to characterise specific T cell immunity following BCG vaccination. These data are critical to determine when to optimally boost BCG induced immunity in infants. We enrolled infants routinely vaccinated with BCG at birth, and determined the frequency of T cells induced by immunisation, at various time points over the first year of life. The T cells were identified by binding of cell surface markers and characterised by cell-specific cytokine production, following 12 hr incubation of infant whole blood with BCG. Multiparameter flow cytometry was used for the analysis. We found that the peak vaccine induced CD4+ T cell response occurred at 10 weeks, followed by a contraction phase. BCG specific CD4+ T cells became more poly functional, and acquired the profile of long-lived T cells (measured by Bcl-2 expression), over the first year of life.

Includes bibiliographical references.