Research Newborn bacille Calmette-Guérin vaccination induces robust infant interferon-γ-expressing natural killer cell responses to mycobacteria

SATVI researchers Melissa Murphy, Elisa Nemes, Professors Mark Hatherill, Tom Scriba, and Libby Briel, Helen Veldtsman, Nondumiso Khomba, Hadn Africa, Marcia Steyn have co-authored "Newborn bacille Calmette-Guérin vaccination induces robust infant interferon-γ -expressing natural killer cell responses to mycobacteria" appearing in the International Journal of Infectious Diseases.

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.

In this study 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 clusters of differentiation (CD)4⁺ T, myeloid, and NK cell responses were measured by flow cytometry; the levels of secreted cytokines were measured by a multiplex bead array.

The study found that newborn BCG vaccination was associated with significantly higher frequencies of BCG-reactive, cytokine-expressing CD4⁺ T cells, and interferon (IFN)-γ-expressing NK cells than in unvaccinated infants but no differences in cytokine-expressing CD33⁺ myeloid cells were observed. The induction of BCG-reactive IFN-γ-expressing NK cells was not associated with the markers of NK cell maturation, differentiation, or cytokine receptor expression. BCG-reactive NK cell responses correlated directly with the levels of secreted interleukin (IL)-2 and IFN-γ and the innate pro-inflammatory cytokines IL-6, IL-1β, and tumor necrosis factor (TNF) in BCG-vaccinated infants only.

The researchers showed that BCG-reactive IFN-γ-expressing NK cells are strongly induced by BCG vaccination in infants and are likely amplified through bystander cytokines.

Keywords: BCG vaccination; Infant; NK cells, Myeloid cells; Tuberculosis.

Citation: Murphy M, Suliman S, Briel L, Veldtsman H, Khomba N, Africa H, Steyn M, Snyders CI, van Rensburg IC, Walzl G, Chegou NN, Hatherill M, Hanekom WA, Scriba TJ, Nemes E. 2023. Newborn bacille Calmette-Guérin vaccination induces robust infant interferon-γ-expressing natural killer cell responses to mycobacteria. International Journal of Infectious Diseases, 25:S1201-9712(23)00069-3. Read publication.