Novel Oral Polio Vaccines Demonstrate Safety and Efficacy in First-in-Human Phase 1 Trial
Key Insights
Novel type 1 and type 3 oral poliovirus vaccines (nOPV1 and nOPV3 (search)) showed strong safety profiles with no serious adverse events in a Phase 1 trial of 205 healthy adults.
The genetically stabilized vaccines achieved seroconversion rates of 86-100% and demonstrated comparable immune responses to existing Sabin-strain vaccines.
These vaccines are designed to reduce risks of vaccine-derived polioviruses and vaccine-associated paralytic poliomyelitis (search) while supporting global polio eradication efforts.
A first-in-human Phase 1 trial has demonstrated that novel type 1 and type 3 oral poliovirus vaccines (nOPV1 and nOPV3 (search)) are safe, well-tolerated, and immunogenic in healthy adults, marking a significant step forward in global polio eradication efforts. The multicentre, observer-masked, randomized controlled trial enrolled 205 vaccinated participants across four USA sites between May 2021 and February 2023.
Enhanced Safety Profile with Genetic Stabilization
The novel vaccines represent genetically stabilized versions of the Sabin-strain monovalent oral poliovirus vaccines (mOPV1 and mOPV3 (search)), specifically developed to reduce the risks associated with vaccine-derived polioviruses and vaccine-associated paralytic poliomyelitis (search). The trial revealed no serious adverse events across all participants, with most side effects being mild in nature.
Severe solicited events occurred in only 1-4% of participants, with fatigue being the predominant symptom. A small number of severe unsolicited adverse events were reported, including abdominal pain, headache, and myalgia in nOPV1 recipients, and one kidney infection in an mOPV1 recipient.
Strong Immunogenic Response
The vaccines demonstrated robust immunological performance, with homotypic seroprotection rates reaching nearly universal levels at baseline and achieving 100% protection 28 days post-vaccination. Seroconversion rates following a single dose were notably high, ranging from 86-100% for nOPV compared to 86-93% for mOPV.
"This first-in-human trial of nOPV1 and nOPV3 (search) showed that both vaccine candidates are safe and well tolerated in healthy adults and can elicit neutralising antibody responses similar to those elicited by mOPV1 and mOPV3 (search), respectively," said researchers from the University of North Carolina and collaborating institutions.
Comparable Viral Shedding Patterns
Faecal viral shedding patterns between the novel vaccines and existing Sabin-strain vaccines were comparable, with peak detection by PCR reaching 100% on Day 8 among participants with prior inactivated poliovirus vaccine (IPV) exposure. Importantly, the magnitude and duration of nOPV shedding were not higher than with Sabin controls.
The study design stratified participants by previous polio vaccination history. Those with prior IPV exposure received a single dose of either nOPV or mOPV, while participants with a history including oral polio vaccine received two doses administered 28 days apart. Researchers observed a reduction of shedding following the second dose, which is consistent with enhancement of intestinal immunity.
Supporting Global Eradication Strategy
The successful deployment of nOPV2 to combat type 2 circulating vaccine-derived polioviruses (VDPVs) has suggested that novel vaccines could be effective in controlling circulating VDPV outbreaks after the cessation of vaccines containing Sabin-strain types 1 and 3 polioviruses.
These nOPVs can support the Global Polio Eradication Initiative (search)'s Polio Endgame Strategy by providing vaccines less likely to be associated with vaccine-associated paralytic polio and the seeding of new circulating vaccine-derived polioviruses (VDPVs).
Path Forward to Phase 2 Studies
The findings indicate that nOPV1 and nOPV3 (search) match the safety, immunogenicity, and shedding profile of existing Sabin-strain vaccines while offering improved genetic stability. "The safety and immunogenicity evidence generated for nOPV1 and nOPV3 in this phase 1 clinical study were sufficient to justify the now ongoing phase 2 studies in geographically relevant target populations of previously vaccinated children and infants, as well as vaccine-naive neonates," the researchers concluded.
The results provide a strong rationale for advancing both candidates into larger Phase 2 trials, representing a crucial advancement in the development of safer oral polio vaccines for global immunization programs.