Bacillus Calmette-Guérin vaccination at birth and in vitro cytokine responses to non-specific stimulation. A randomized clinical trial

Eur J Clin Microbiol Infect Dis. 2018 Jan;37(1):29-41. doi: 10.1007/s10096-017-3097-2. Epub 2017 Sep 10.


Several studies have shown increased in vitro cytokine responses to non-related pathogens after Bacillus Calmette-Guérin (BCG) vaccination. A total of 158 infants (80 BCG administered within 7 days of birth; 78 controls) were bled 4 days post-randomization, and at age 3 and 13 months. Geometric mean concentrations of IL-1β, TNF-α, IL-6 (24 h stimulation) and IFN-γ, IL-10, IL-17, IL-22 (96 h stimulation) in response to in vitro stimulation with RPMI, LPS, PHA, Escherichia coli, Streptococcus pneumoniae, Candida albicans and BCG were compared among BCG vaccinated children and controls. BCG vaccination did not affect in vitro cytokine production, except IFN-γ and IL-22 response to BCG. Stratifying for 'age at randomization' we found a potentiating effect of BCG on cytokine production (TNF-α, IL-6, IL-10) in the 4 days post randomization stimulations, among children who were vaccinated at age 2-7 days versus age 0-1 days. BCG vaccination did not potentiate cytokine production to non-BCG antigens. At 4 days post randomization, BCG was associated with higher cytokine production in the later randomized children.

Keywords: Bacillus Calmette-Guérin; Cytokine response; Heterolougus immunity; Infants; Randomized clinical trial; Trained immunity; Vaccines.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • BCG Vaccine / administration & dosage
  • BCG Vaccine / immunology*
  • Candida albicans / immunology
  • Cytokines / blood*
  • Escherichia coli / immunology
  • Female
  • Humans
  • Infant, Newborn
  • Male
  • Mycobacterium bovis / immunology*
  • Streptococcus pneumoniae / immunology
  • Vaccination


  • BCG Vaccine
  • Cytokines