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The predicted titre was calculated assuming an exponential decay from baseline with a half-life of 28 days. Statistical analysis We selected a sample size of 220 participants BAY-545 in the nOPV2 group, with a placebo control group with half that number of participants (n=110), to provide sufficient power to assess the immunogenicity of the candidate vaccines on the basis of previous studies. nOPV2 or placebo, administered at age 0C3 days and at 4 weeks. Exclusion criteria included receipt of rotavirus or any other poliovirus vaccine, any infection or illness at the time of enrolment (vomiting, diarrhoea, or intolerance to liquids), diagnosis or suspicion of any immunodeficiency disorder in the infant or a close family member, or any contraindication for venipuncture. The primary safety outcome was safety and tolerability after one and two doses of nOPV2, given 4 weeks apart in poliovirus vaccine-naive newborn infants and the primary immunogenicity outcome was the seroconversion rate for neutralising antibodies against type 2 poliovirus, measured 28 days after the first and second vaccinations with nOPV2. Study staff recorded solicited and unsolicited adverse events after each dose during daily home visits for 7 days. Poliovirus neutralising antibody responses were measured in sera drawn at birth and at age 4 weeks and 8 weeks. This study is registered on ClinicalTrials.gov, “type”:”clinical-trial”,”attrs”:”text”:”NCT04693286″,”term_id”:”NCT04693286″NCT04693286. Findings Between Sept 21, 2020, and Aug 16, 2021, we screened 334 newborn infants, of whom three (<1%) were found to be ineligible and one (<1%) was withdrawn by the parents; the remaining 330 (99%) infants were assigned to receive nOPV2 (n=220 [67%]) or placebo (n=110 [33%]). nOPV2 was well tolerated; 154 (70%) of 220 newborn infants in the nOPV2 group and 78 (71%) of 110 in the placebo group had solicited adverse events, which were all mild or moderate in severity. Severe unsolicited adverse events in PRKCA 11 (5%) vaccine recipients and five (5%) placebo recipients were considered unrelated to vaccination. 306 (93%) of 330 infants had seroprotective maternal antibodies against type 2 poliovirus at birth, decreasing to 58 (56%) BAY-545 of 104 in the placebo group at 8 weeks. BAY-545 In the nOPV2 group 196 (90%) of 217 infants seroconverted by week 8 after two doses, when 214 (99%) had seroprotective antibodies. Interpretation nOPV2 was well tolerated and immunogenic in newborn infants, with two doses, at birth and 4 weeks, resulting in almost 99% of infants having protective neutralising antibodies. Funding Bill & Melinda Gates Foundation. Introduction Although live oral poliovirus vaccines (OPVs) are safe and effective and have led to the elimination of poliomyelitis from most of the world, in rare circumstances the attenuated viruses in OPVs can mutate and reacquire neurovirulence. This mutation can result in vaccine-associated paralytic polio in vaccine recipients and susceptible close contacts and, in settings of persistently poor BAY-545 immunisation coverage, can lead to the emergence of circulating vaccine-derived polioviruses (cVDPVs).1 Following the global eradication of wild-type 2 poliovirus, the risk of vaccine-associated paralytic polio and cVDPVs led to the global withdrawal of type 2 virus from OPVs for routine use in April, 2016, with a switch to use of bivalent OPVs containing only types 1 and 3.2 Since this switch routine immunisation against type 2 poliovirus has been exclusively through the use of trivalent inactivated poliovirus vaccines (IPVs). However, despite the switch and cessation of routine use of live type 2 OPVs (OPV2), type 2 cVDPV (cVDPV2) outbreaks have occurred in many countries, resulting in cases of acute flaccid paralysis, which represent the majority of such polio cases worldwide.3 Because IPVs alone, the only existing source of protection against type 2 poliovirus in routine immunisation, induce minimal intestinal immunity, these vaccines are ineffective in preventing faecalCoral transmission in settings of poor hygiene and sanitation.4 The only way to contain cVDPV2 outbreaks in such settings is to use stockpiled monovalent OPV2 vaccine, which itself risks propagating new cVDPVs. A novel OPV2 (nOPV2) is an important new addition to outbreak control tools. nOPV2 has been genetically designed with attenuating modifications and shown to have a lower risk BAY-545 of reversion to neurovirulence compared with the Sabin vaccine, but with non-inferior immunogenicity in adults and children.5, 6, 7 Research in context Evidence before this study Outbreaks of circulating vaccine-derived poliovirus type 2 (cVDPV2) are now the main cause of paralytic poliomyelitis worldwide. A novel, genetically more stable monovalent type.