Safety and immunogenicity of shorter interval schedules of the novel oral poliovirus vaccine type 2 in infants: a phase 3, randomised, controlled, non-inferiority study in the Dominican Republic

Background The novel oral poliovirus vaccine type 2 (nOPV2) is now authorised by a WHO emergency use listing and widely distributed to interrupt outbreaks of circulating vaccine -derived poliovirus type 2. As protection of vulnerable populations, particularly young infants, could be facilitated by shorter intervals between the two recommended doses, we aimed to assess safety and non -inferiority of immunogenicity of nOPV2 in 1 -week, 2 -week, and 4 -week schedules. Methods In this phase 3, open -label, randomised trial, healthy, full -term, infants aged 6-8 weeks from a hospital or a clinic in the Dominican Republic were randomly allocated (1:1:1 ratio) using a pre -prepared, computer -generated randomisation schedule to three groups to receive two doses of nOPV2 immunisations with a 1 -week interval (group A), 2 -week interval (group B), or 4 -week interval (group C). The nOPV2 vaccine was given at a 0 center dot 1 mL dose and contained at least 105 50% cell culture infective dose. Neutralising antibodies against poliovirus types 1, 2, and 3 were measured before each immunisation and 4 weeks after the second dose. The primary outcome was the type 2 seroconversion rate 28 days after the second dose, and the non -inferiority margin was defined as a lower bound 95% CI of greater than -10%. Safety and reactogenicity were assessed through diary cards completed by the parent or guardian. The trial is registered with ClinicalTrials.gov, NCT05033561. Findings We enrolled 905 infants between Dec 16, 2021, and March 28, 2022. 872 infants were included in the perprotocol analyses: 289 in group A, 293 in group B, and 290 in group C. Type 2 seroconversion rates were 87 center dot 5% (95% CI 83 center dot 2 to 91 center dot 1) in group A (253 of 289 participants), 91 center dot 8% (88 center dot 1 to 94 center dot 7) in group B (269 of 293 participants), and 95 center dot 5% (92 center dot 5 to 97 center dot 6) in group C (277 of 290 participants). Non -inferiority was shown for group B compared with group C (difference in rates -3 center dot 7; 95% CI -7 center dot 9 to 0 center dot 3), but not for group A compared with group C (-8 center dot 0; -12 center dot 7 to -3 center dot 6). 4 weeks after the second nOPV2 dose, type 2 neutralising antibodies increased in all three groups such that over 95% of each group was seroprotected against polio type 2, although final geometric mean titres tended to be highest with longer intervals between doses. Immunisation with nOPV2 was well tolerated with no causal association to vaccination of any severe or serious adverse event; one death from septic shock during the study was unrelated to the vaccine. Interpretation Two nOPV2 doses administered 1 week or 2 weeks apart from age 6 weeks to 8 weeks were safe and immunogenic. Immune responses after a 2 -week interval were non -inferior to those after the standard 4 -week interval, but marked responses after a 1 -week interval suggest that schedules with an over 1 -week interval can be used to provide flexibility to campaigns to improve coverage and hasten protection during circulating vaccine -derived poliovirus type 2 outbreaks. Funding Bill & Melinda Gates Foundation. Copyright (c) 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.