Intestinal mucosal immune responses induced by novel oral poliovirus vaccine type 2 and Sabin monovalent oral poliovirus vaccine type 2: an analysis of data from four clinical trials

BACKGROUND: A novel oral polio vaccine type 2 (nOPV2), which is more genetically stable (ie, lower risks of reverting to neurovirulence) than the Sabin monovalent OPV2 (mOPV2), has been deployed to interrupt circulating vaccine-derived poliovirus type 2 (PV2) outbreaks. This study compares intestinal mucosal immune responses induced by nOPV2 and mOPV2. METHODS: In this analysis, we evaluated intestinal mucosal immune responses in healthy participants of different ages (ie, infants aged 18-22 weeks, children aged 1-4 years, and adults aged 18-50 years) and vaccine backgrounds (ie, OPV2-experienced vs OPV2-naive). Participants were selected from two phase 2 trials of nOPV2, conducted in 2018-19 (infants and children, NCT03554798 Panama; adults, EudraCT 2018-001684-22-NCT04544787 Belgium), and two phase 4 historical control trials of mOPV2, conducted in 2015-16 (infants and children, NCT02521974 Panama; adults, EudraCT 2015-003325-33 Belgium). We measured PV2-specific neutralising activity and IgA concentrations in stools collected before and 14 days after vaccination. FINDINGS: neutralisation titres (1 IQR 1-1 vs 1 1-1·5, p=0·89) on day 14, a smaller percentage of OPV2-experienced adults shed vaccine virus than OPV2-naive adults upon nOPV2 challenge (20% vs 82%, p<0·0001). INTERPRETATION: We found no evidence of differences in the intestinal mucosal immune responses induced by nOPV2 or Sabin mOPV2 and observed the strongest responses in infants. FUNDING: The Bill & Melinda Gates Foundation, Japan Agency for Medical Research and Development.