A FIRST-in-human trial has shown that novel type 1 and type 3 oral poliovirus vaccines (nOPV1 and nOPV3) are safe, well tolerated, and immunogenic in healthy adults, supporting their advancement to Phase 2 studies.
Developed to reduce the risks associated with vaccine-derived polioviruses and vaccine-associated paralytic poliomyelitis, nOPV1 and nOPV3 are genetically stabilised versions of the Sabin-strain monovalent oral poliovirus vaccines (mOPV1 and mOPV3). In a multicentre, observer-masked, randomised controlled Phase 1 trial conducted across four USA sites, researchers assessed safety and immunogenicity in adults stratified by previous polio vaccination history. Participants with prior inactivated poliovirus vaccine (IPV) exposure received a single dose of either nOPV or mOPV, while those with a history including oral polio vaccine received two doses 28 days apart. The trial enrolled 205 vaccinated participants between May 2021–February 2023.
No serious adverse events were observed. Most side-effects were mild, and severe solicited events occurred in only 1–4% of participants, predominantly fatigue. A small number of severe unsolicited adverse events were reported, including abdominal pain, headache, and myalgia in nOPV1 recipients, and a kidney infection in one mOPV1 recipient. Homotypic seroprotection rates were almost universal at baseline and reached 100% 28 days post-vaccination. Seroconversion rates following a single dose were high, ranging from 86–100% for nOPV and 86–93% for mOPV. Faecal viral shedding patterns were also comparable between groups, with peak detection by PCR at 100% on Day 8 among IPV participants.
These findings indicate that nOPV1 and nOPV3 match the safety, immunogenicity, and shedding profile of existing Sabin-strain vaccines, while offering improved genetic stability. The results provide a strong rationale for advancing both candidates into larger Phase 2 trials.
Reference
Mercer LD et al. Safety and immunogenicity of novel live attenuated type 1 and type 3 oral poliomyelitis vaccines in healthy adults in the USA: a first-in-human, observer-masked, multicentre, phase 1 randomised controlled trial. Lancet Infect Dis. 2025; DOI:10.1016/S1473-3099(25)00285-3.
