The genomic landscape of monocytes and CD4+ T cells after BCG vaccination in Malawian infants

The Bacille Calmette-Guérin (BCG) vaccine administration studies in human adults determined that BCG-mediated mechanisms of protection include epigenetic reprogramming of innate immune cells and heterologous T cell immunity. The current study aimed to confirm that BCG immunization similarly impacts the functionally distinct infant immune system. Towards this goal, we applied RNA sequencing to assess molecular changes in circulating monocytes and CD4+ T cells of Malawian infants prior to and 2 to 13 weeks after BCG immunization. We identified 168 differentially expressed genes (DEGs), 14 upregulated and 152 downregulated, in monocytes after BCG vaccination. The upregulated monocyte DEGs were enriched in genes associated with metabolic pathways, in particular glycolysis and lipid metabolism. In CD4 T cells, 322 DEGs (95 upregulated and 226 downregulated) were identified after BCG vaccination, and these DEGs were representative of activation, proliferation, differentiation, and cell survival. These findings are consistent with data reported in BCG vaccinated adults and contribute to the understanding of molecular changes in monocytes and CD4 T cells that may explain the improved capacity of the infant immune system to respond to pathogens after BCG vaccination.