The immunological effects of oral polio vaccine provided with BCG vaccine at birth: a randomised trial

Vaccine. 2014 Oct 14;32(45):5949-56. doi: 10.1016/j.vaccine.2014.08.062. Epub 2014 Sep 16.

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.

Conclusion: The results corroborate that OPV attenuates the immune response to co-administered BCG at birth.

Keywords: Bacillus Calmette-Guérin; Heterologous immunity; Infant; NCT00710983; Non-specific effect; Oral polio vaccine.

Publication types

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

MeSH terms

  • BCG Vaccine / administration & dosage*
  • BCG Vaccine / immunology*
  • Cytokines / immunology
  • Female
  • Guinea-Bissau
  • Humans
  • Infant, Newborn
  • Interferon-gamma / immunology*
  • Male
  • Poliovirus Vaccine, Oral / administration & dosage*
  • Poliovirus Vaccine, Oral / immunology*

Substances

  • BCG Vaccine
  • Cytokines
  • IFNG protein, human
  • Poliovirus Vaccine, Oral
  • Interferon-gamma