The Bacille Calmette-Guérin (BCG) vaccine is usually administered at birth to protect against severe forms of tuberculosis in children. BCG also confers some protection against other infections, possibly mediated by innate immune training. We investigated whether newborn BCG vaccination modulates myeloid and natural killer (NK) cell responses to mycobacteria.
BCG vaccination was either administered at birth or delayed to 6 or 10 weeks of age in 130 South African infants. Whole blood was stimulated with BCG and CD4 T, myeloid and NK cell responses measured by flow cytometry; levels of secreted cytokines were measured by multiplex bead array.
Newborn BCG vaccination was associated with significantly higher frequencies of BCG-reactive, cytokine-expressing CD4 T cells and IFNγ-expressing NK cells, compared with unvaccinated infants, but no differences in cytokine-expressing CD33 myeloid cells were observed. Induction of BCG-reactive IFNγ-expressing NK cells was not associated with markers of NK cell maturation, differentiation or cytokine receptor expression. BCG-reactive NK cell responses correlated directly with levels of secreted IL-2 and IFNγ and the innate pro-inflammatory cytokines IL-6, IL-1β and TNF in BCG vaccinated infants only.
We showed that BCG-reactive IFNγ-expressing NK cells are strongly induced by BCG vaccination in infants and are likely amplified through by-stander cytokines.

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