title: Heterologous immunological effects of early BCG vaccination in low-birth-weight infants in Guinea-Bissau: a randomized-controlled trial.
abstract: BACKGROUND
  Bacillus Calmette-Guérin (BCG) seems to have beneficial nonspecific effects; early BCG vaccination of low-birth-weight (LBW) newborns reduces neonatal mortality by >40% due to prevention of primarily septicemia and pneumonia.
  
  
  METHODS
  Within a randomized trial in LBW infants in Guinea-Bissau of early BCG vs the usual postponed BCG, a subgroup was bled 4 weeks after randomization. Levels of interleukin (IL)-1β, IL-5, IL-6, IL-10, IL-17, interferon (IFN)-γ and tumor necrosis factor (TNF)-α were measured from whole-blood assays stimulated with innate agonists to Toll-like receptor (TLR)-2, -4 or -7/8, or purified protein derivative (PPD).
  
  
  RESULTS
  Among 467 infants, BCG significantly increased the in vitro cytokine responses to purified protein derivative of Mycobacterium tuberculosis (PPD), as expected. BCG was also associated with increased responses to heterologous innate stimulation, particularly of the cytokines IL-1β, IL-6, TNF-α, and IFN-γ.
  
  
  CONCLUSIONS
  Four weeks after immunization, BCG-vaccinated infants have a significantly increased production of cytokines upon heterologous challenge, particularly T helper cell type 1 polarizing and typically monocyte-derived pro-inflammatory cytokines. BCG may accelerate the development of the neonatal immune system, mediating comprehensive protection against infections and mortality.
authors.affiliation: Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Copenhagen, Department of Cardiovascular and Renal Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark Projécto de Saúde Bandim, Indepth Network, codex 1004, Bissau, Guinea-Bissau.
authors.forename: Kristoffer Jarlov
authors.initials: KJ
authors.lastname: Jensen
authors.affiliation: Danish Centre for Neonatal Screening, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Nanna
authors.initials: N
authors.lastname: Larsen
authors.affiliation: Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Copenhagen.
authors.forename: Sofie
authors.initials: S
authors.lastname: Biering-Sørensen
authors.affiliation: Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Copenhagen.
authors.forename: Andreas
authors.initials: A
authors.lastname: Andersen
authors.affiliation: Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Copenhagen.
authors.forename: Helle Brander
authors.initials: HB
authors.lastname: Eriksen
authors.affiliation: Projécto de Saúde Bandim, Indepth Network, codex 1004, Bissau, Guinea-Bissau.
authors.forename: Ivan
authors.initials: I
authors.lastname: Monteiro
authors.affiliation: Danish Centre for Neonatal Screening, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: David
authors.initials: D
authors.lastname: Hougaard
authors.affiliation: Projécto de Saúde Bandim, Indepth Network, codex 1004, Bissau, Guinea-Bissau.
authors.forename: Peter
authors.initials: P
authors.lastname: Aaby
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.affiliation: Department of Immunology, Monash University, Melbourne, Australia.
authors.forename: Katie L
authors.initials: KL
authors.lastname: Flanagan
authors.affiliation: Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Copenhagen, Projécto de Saúde Bandim, Indepth Network, codex 1004, Bissau, Guinea-Bissau OPEN, University of Southern Denmark/Odense University Hospital.
authors.forename: Christine Stabell
authors.initials: CS
authors.lastname: Benn
mesh_terms: D001500:BCG Vaccine / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006169:Guinea-Bissau; D006801:Humans; D007223:Infant; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D008297:Male; D012621:Seasons; D012737:Sex Factors; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D014611:Vaccination
chemical_list: D001500:BCG Vaccine; D016207:Cytokines
keywords: Africa; BCG; cytokines; heterologous immunity; infants; nonspecific effects