Gamma-irradiated bacille Calmette-Guérin vaccination does not modulate the innate immune response during experimental human endotoxemia in adult males

J Immunol Res. 2015:2015:261864. doi: 10.1155/2015/261864. Epub 2015 Mar 26.


Bacille Calmette-Guérin (BCG) vaccine exerts nonspecific immunostimulatory effects and may therefore represent a novel therapeutic option to treat sepsis-induced immunoparalysis. We investigated whether BCG vaccination modulates the systemic innate immune response in humans in vivo during experimental endotoxemia. We used inactivated gamma-irradiated BCG vaccine because of the potential risk of disseminated disease with the live vaccine in immunoparalyzed patients. In a randomized double-blind placebo-controlled study, healthy male volunteers were vaccinated with gamma-irradiated BCG (n = 10) or placebo (n = 10) and received 1 ng/kg lipopolysaccharide (LPS) intravenously on day 5 after vaccination to assess the in vivo immune response. Peripheral blood mononuclear cells were stimulated with various related and unrelated pathogens 5, 8 to 10, and 25 to 35 days after vaccination to assess ex vivo immune responses. BCG vaccination resulted in a scar in 90% of vaccinated subjects. LPS administration elicited a profound systemic immune response, characterized by increased levels of pro- and anti-inflammatory cytokines, hemodynamic changes, and flu-like symptoms. However, BCG modulated neither this in vivo immune response, nor ex vivo leukocyte responses at any time point. In conclusion, gamma-irradiated BCG is unlikely to represent an effective treatment option to restore immunocompetence in patients with sepsis-induced immunoparalysis. This trial is registered with NCT02085590.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • BCG Vaccine / immunology*
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Double-Blind Method
  • Endotoxemia / drug therapy*
  • Endotoxemia / immunology
  • Humans
  • Immunity, Innate / immunology*
  • Leukocytes, Mononuclear / immunology
  • Lipopolysaccharides / administration & dosage
  • Lipopolysaccharides / immunology*
  • Lymphocyte Activation / immunology
  • Male
  • Mycobacterium bovis / immunology
  • Placebos
  • Vaccination


  • BCG Vaccine
  • Cytokines
  • Lipopolysaccharides
  • Placebos

Associated data