Comparison of immune responses induced by Bacillus calmette-Guerin when given at birth or at 6 weeks of age in Ugandan Infants

Doctoral Thesis


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University of Cape Town

In Uganda, infants delivered at a health care facility receive the tuberculosis vaccine Bacillus Calmette-Guerin (BCG) on the first day of life. Infants delivered at home receive BCG at their first health care facility visit at 6 weeks of age. Our aim was to determine the effect of this delay in BCG administration on the induced immune response. Our hypothesis was that infants who received BCG at 6 weeks of age would show an enhanced BCG-induced T cell immunity compared to infants vaccinated at birth. We optimised several polychromatic flow cytometry reagent panels to compare BCG-specific immunity in 9 months-old infants who had received the vaccine either at birth or at 6 weeks of age. We used a 12-hour whole blood intracellular cytokine/cytotoxic marker assay to measure T cell-associated cytokine expression and memory phenotypes. We also compared the capacity of BCGspecific T cells to proliferate and produce cytokines upon antigenic stimulation with a 6-day proliferation assay. Finally, we measured plasma soluble cytokines levels in the two groups of infant using multiplex assay. We enrolled 92 infants: 50 had received BCG at birth and 42 at 6 weeks of age. BCG induced predominantly CD4⁺ T cell responses, and lesser CD8⁺ T cell responses, in both groups. Birth vaccination was associated with greater induction of CD4⁺ and CD8⁺ T cells expressing either IFN-γ alone, or IFN-γ together with perforin, compared with delayed vaccination. Further, birth vaccination induced proliferating cells that had greater capacity to produce IFN-γ, TNF-α and IL-2 together, compared with delayed vaccination. In conclusion, distinct patterns of T cell induction occurred when BCG was given at birth and at 6 weeks of age. We propose that this diversity might impact protection against tuberculosis. Our results differ from those of delayed BCG vaccination studies in South Africa and the Gambia, suggesting geographical and population heterogeneity may affect BCG-induced T cell response.

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