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: We compared data from 160 participants (ie, 47 infants, 47 children, and 66 adults) in the nOPV2 trials to 188 participants (ie, 42 infants, 46 children, and 100 adults) in the mOPV2 trials. Within each age group, one dose of nOPV2 or mOPV2 induced similar intestinal PV2-specific neutralisation and IgA responses on day 14. Responses diminished with age: among the OPV2-naive participants who received nOPV2, 27 (82%) of 33 infants, 17 (61%) of 28 children, and four (25%) of 16 adults had detectable PV2-specific neutralisation on day 14. Despite having similar median log<inf>10</inf> IgA responses (1·4 [IQR 1·0–2·2] vs 1·4 [1·1–1·7], p=0·34) and median log<inf>2</inf> 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.