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

D L Jeppesen, O Pryds, C S Benn, M G Netea, M Ruhwald, P Aaby, L G Stensballe, P-E Kofoed, S D Nielsen, T N Nissen, T Hoffmann, L M Thøstesen, J Kjærgaard, A Andersen, R J W Arts, B A Blok, N M Birk

Journal: European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology 2018;37(1):29-41

PMID: 28890996

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Abstract

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.

Address: Department of Pediatrics, 460, Copenhagen University Hospital, Kettegaard Allé 30, DK-2650, Hvidovre, Denmark. [email protected].; Department of Pediatrics, 460, Copenhagen University Hospital, Kettegaard Allé 30, DK-2650, Hvidovre, Denmark.; Division of Experimental Internal Medicine, Department of Internal Medicine, Radboud University Medical Center and Radboud Center for Infectious Diseases, Geert Grooteplein 10, 6525GA, Nijmegen, The Netherlands.; Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Artillerivej 5, DK-2300, Copenhagen S, Denmark.; Odense Patient data Explorative Network, Odense University Hospital/Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.; The Child and Adolescent Clinic 4072, Juliane Marie Centret, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100, Copenhagen Ø, Denmark.; Department of Pediatrics, Kolding Hospital, Skovvangen 2-8, DK-6000, Kolding, Denmark.; Viro-immunology Research Unit, Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100, Copenhagen Ø, Denmark.; Human Immunology, Infectious Disease Immunology, Division of Vaccine, Statens Serum Institut, DK-2300, Artillerivej 5, Denmark.

DOI: 10.1007/s10096-017-3097-2

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MeSH Terms: BCG Vaccine, Candida albicans, Cytokines, Escherichia coli, Female, Humans, Infant, Newborn, Male, Mycobacterium bovis, Streptococcus pneumoniae, Vaccination