title: The immunological effects of oral polio vaccine provided with BCG vaccine at birth: a randomised trial.
abstract: BACKGROUND
  Vaccines may have non-specific effects. An observational study from Guinea-Bissau suggested that oral polio vaccine at birth (OPV0) provided with Bacillus Calmette-Guérin (BCG) vaccine was associated with down-regulation of the immune response to BCG vaccine 6 weeks later. Based on the previous finding, we wanted to test our a priori hypothesis that OPV would dampen the immune response to BCG, and secondarily to test immune responses to other antigens.
  
  
  METHODS
  The study was conducted at the Bandim Health Project in Guinea-Bissau in 2009-2010. Infants were randomised to OPV0+BCG versus BCG alone at birth, and subsequently randomised to have a blood sample taken at 2, 4 or 6 weeks post-randomisation. Excreted levels of cytokines (IL-2, IL-5, IL-10, TNF-α and IFN-γ) were measured from whole blood in vitro stimulations with a panel of recall vaccine antigens (BCG, PPD, OPV), mitogen (PHA) or innate agonists (LPS, Pam3cys, PolyI:C). Additionally, we measured the local reaction to BCG, white blood cell distribution, C-reactive protein (CRP) and retinol-binding protein (RBP). Cytokine production was analysed as the prevalence ratios of responders above the median.
  
  
  RESULTS
  Blood samples from 430 infants (209 OPV0+BCG; 221 BCG alone) were analysed. There were no strong differences in effects 2, 4 and 6 weeks post-randomisation and subsequent analyses were performed on the pooled data. As hypothesised, receiving OPV0+BCG versus BCG alone was associated with significantly lower prevalence of IFN-γ responses to PPD (prevalence ratio (PR): 0.84 (0.72-0.98)) and reduced IL-5 to PPD (PR: 0.78 (0.64-0.96)). No effects were observed for CPR, RBP, white blood cell distribution, or BCG scar prevalence.
  
  
  CONCLUSIONS
  The results corroborate that OPV attenuates the immune response to co-administered BCG at birth.
authors.affiliation: Research Center for Vitamins & Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark; Department of Cardiovascular and Renal Research, Faculty of Health Sciences, University of Southern Denmark, J.B. Winsløws Vej 25, 3, DK-5000 Odense C, Denmark; Bandim Health Project, INDEPTH Network, Apartado 861, 1004 Bissau codex, Guinea-Bissau. Electronic address: kjj@ssi.dk.
authors.forename: Kristoffer Jarlov
authors.initials: KJ
authors.lastname: Jensen
authors.affiliation: Research Center for Vitamins & Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark; Bandim Health Project, INDEPTH Network, Apartado 861, 1004 Bissau codex, Guinea-Bissau; Biopharmaceutical Research Unit, Novo Nordisk A/S, Novo Nordisk Park 1, DK-2760 Måløv, Denmark.
authors.forename: Hanne Sophie
authors.initials: HS
authors.lastname: Karkov
authors.affiliation: Research Center for Vitamins & Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark.
authors.forename: Najaaraq
authors.initials: N
authors.lastname: Lund
authors.affiliation: Research Center for Vitamins & Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark.
authors.forename: Andreas
authors.initials: A
authors.lastname: Andersen
authors.affiliation: Research Center for Vitamins & Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark.
authors.forename: Helle Brander
authors.initials: HB
authors.lastname: Eriksen
authors.affiliation: Bandim Health Project, INDEPTH Network, Apartado 861, 1004 Bissau codex, Guinea-Bissau.
authors.forename: Amarildo Gomes
authors.initials: AG
authors.lastname: Barbosa
authors.affiliation: Microbiological Diagnostics & Virology, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark.
authors.forename: Bjørn
authors.initials: B
authors.lastname: Kantsø
authors.affiliation: Bandim Health Project, INDEPTH Network, Apartado 861, 1004 Bissau codex, Guinea-Bissau.
authors.forename: Peter
authors.initials: P
authors.lastname: Aaby
authors.affiliation: Research Center for Vitamins & Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark; Odense Patient data Explorative Network, Institute of Clinical Research, University of Southern Denmark/Odense University Hospital, J.B. Winsløws Vej 25, 3, DK-5000 Odense C, Denmark.
authors.forename: Christine Stabell
authors.initials: CS
authors.lastname: Benn
mesh_terms: D001500:BCG Vaccine / Q000008:administration & dosage* / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D005260:Female; D006169:Guinea-Bissau; D006801:Humans; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000276:immunology*; D008297:Male; D011055:Poliovirus Vaccine, Oral / Q000008:administration & dosage* / Q000276:immunology*
chemical_list: D001500:BCG Vaccine; D016207:Cytokines; C573415:IFNG protein, human; D011055:Poliovirus Vaccine, Oral; D007371:Interferon-gamma
keywords: Bacillus Calmette-Guérin; Heterologous immunity; Infant; NCT00710983; Non-specific effect; Oral polio vaccine