title: Gamma-irradiated bacille Calmette-Guérin vaccination does not modulate the innate immune response during experimental human endotoxemia in adult males.
abstract: 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.
authors.affiliation: Department of Intensive Care Medicine, Radboud University Medical Center, Radboud Center for Infectious Diseases (RCI), P.O. Box 9101, 6500 HB Nijmegen, Netherlands ; Department of Internal Medicine, Radboud University Medical Center, Radboud Center for Infectious Diseases (RCI), P.O. Box 9101, 6500 HB Nijmegen, Netherlands.
authors.forename: Linda A C
authors.initials: LA
authors.lastname: Hamers
authors.affiliation: Department of Intensive Care Medicine, Radboud University Medical Center, Radboud Center for Infectious Diseases (RCI), P.O. Box 9101, 6500 HB Nijmegen, Netherlands.
authors.forename: Matthijs
authors.initials: M
authors.lastname: Kox
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, Radboud Center for Infectious Diseases (RCI), P.O. Box 9101, 6500 HB Nijmegen, Netherlands.
authors.forename: Rob J W
authors.initials: RJ
authors.lastname: Arts
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, Radboud Center for Infectious Diseases (RCI), P.O. Box 9101, 6500 HB Nijmegen, Netherlands.
authors.forename: Bastiaan
authors.initials: B
authors.lastname: Blok
authors.affiliation: Department of Intensive Care Medicine, Radboud University Medical Center, Radboud Center for Infectious Diseases (RCI), P.O. Box 9101, 6500 HB Nijmegen, Netherlands ; Department of Internal Medicine, Radboud University Medical Center, Radboud Center for Infectious Diseases (RCI), P.O. Box 9101, 6500 HB Nijmegen, Netherlands.
authors.forename: Jenneke
authors.initials: J
authors.lastname: Leentjens
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, Radboud Center for Infectious Diseases (RCI), P.O. Box 9101, 6500 HB Nijmegen, Netherlands.
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.affiliation: Department of Intensive Care Medicine, Radboud University Medical Center, Radboud Center for Infectious Diseases (RCI), P.O. Box 9101, 6500 HB Nijmegen, Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Pickkers
mesh_terms: D000328:Adult; D001500:BCG Vaccine / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004311:Double-Blind Method; D019446:Endotoxemia / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D009163:Mycobacterium bovis / Q000276:immunology; D010919:Placebos; D014611:Vaccination
chemical_list: D001500:BCG Vaccine; D016207:Cytokines; D008070:Lipopolysaccharides; D010919:Placebos