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

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.