Browsing by Author "Mayanja-Kizza, Harriet"
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- ItemOpen AccessComparison of immune responses induced by Bacillus calmette-Guerin when given at birth or at 6 weeks of age in Ugandan Infants(2014) Lutwama, Fredrick; Hanekom, Willem A; Kagina, Benjamin Mugo; Day, Cheryl; Mayanja-Kizza, HarrietIn 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.
- ItemOpen AccessGenetic variation in TLR genes in Ugandan and South African populations and comparison with HapMap data(Public Library of Science, 2012) Baker, Allison R; Qiu, Feiyou; Randhawa, April Kaur; Horne, David J; Adams, Mark D; Shey, Muki; Barnholtz-Sloan, Jill; Mayanja-Kizza, Harriet; Kaplan, Gilla; Hanekom, Willem A; Boom, W Henry; Hawn, Thomas R; Stein, Catherine MGenetic epidemiological studies of complex diseases often rely on data from the International HapMap Consortium for identification of single nucleotide polymorphisms (SNPs), particularly those that tag haplotypes. However, little is known about the relevance of the African populations used to collect HapMap data for study populations conducted elsewhere in Africa. Toll-like receptor (TLR) genes play a key role in susceptibility to various infectious diseases, including tuberculosis. We conducted full-exon sequencing in samples obtained from Uganda (n = 48) and South Africa (n = 48), in four genes in the TLR pathway: TLR2, TLR4, TLR6, and TIRAP. We identified one novel TIRAP SNP (with minor allele frequency [MAF] 3.2%) and a novel TLR6 SNP (MAF 8%) in the Ugandan population, and a TLR6 SNP that is unique to the South African population (MAF 14%). These SNPs were also not present in the 1000 Genomes data. Genotype and haplotype frequencies and linkage disequilibrium patterns in Uganda and South Africa were similar to African populations in the HapMap datasets. Multidimensional scaling analysis of polymorphisms in all four genes suggested broad overlap of all of the examined African populations. Based on these data, we propose that there is enough similarity among African populations represented in the HapMap database to justify initial SNP selection for genetic epidemiological studies in Uganda and South Africa. We also discovered three novel polymorphisms that appear to be population-specific and would only be detected by sequencing efforts.