Two novel type 2 oral poliovirus vaccine (OPV2) candidates were safe, well tolerated, and immunogenic in healthy adults, young children, and infants similar to Sabin monovalent OPV2, according to a couple of studies published in The Lancet.1,2
These 2 randomized, partly-masked studies aimed to address the emergence and spread of circulating vaccine-derived type 2 polioviruses and vaccine-associated paralytic poliomyelitis from Sabin monovalent OPV2. Due to the global withdrawal of Sabin monovalent OPV2 in 2016, both studies conducted a phase 4 prospective historical control study to provide baseline data with monovalent OPV2 and a phase 2 study of 2 novel OPV2 candidates, OPV2-c1 and OPV2-c2.
The primary objective in both studies was to compare the safety and immunogenicity of OPV2-c1 and OPV2-c2 with monovalent OPV2. Immune responses were assessed at baseline, then 28 days after the first and second dose of OPV2-c1 and OPV2-c2. Researchers also evaluated the noninferiority of OPV2-c1 and OPV2-c2 relative to the monovalent OPV2 with a 10% margin for risk difference.
For the study in healthy adults (aged 18-50 years)1, the historical control study included 100 participants who were randomly assigned in a 1:1 ratio to receive either 1 or 2 doses of the monovalent OPV2. In the phase 2 study (ClinicalTrials.gov Identifier: NCT04544787), 200 participants with a history of previous OPV vaccination were randomly assigned to receive 1 or 2 doses of OPV2-c1 or OPV2-c2. An additional 50 participants previously vaccinated with inactivated poliovirus vaccine (IPV) were randomly assigned to receive OPV2-c1, OPV2-c2, or placebo.
In the second study2, researchers conducted 2 single-center, multi-site trials in healthy children aged 1 to 4 years and infants aged 18 to 22 weeks who had been previously immunized with existing vaccines. In the historical control study (ClinicalTrials.gov Identifier: NCT02521974), there were 50 children and 110 infants. Children received 2 doses of monovalent OPV2; all infants received 1 dose of monovalent OPV2 and 50 were randomly assigned to receive a second dose 28 days later.
In the phase 2 study (ClinicalTrials.gov identifier: NCT03554798), 100 children and 574 infants were enrolled. Children received 2 high doses of OPV2-c1 or OPV2-c2 28 days apart and infants received 1 low dose or high dose of OPV2-c1 or OPV2-c2, and 50 were randomly assigned within each subset to receive a second dose 28 days later. Randomization was 1:1 with each dose level, and 1:4 for 1 vs 2 doses until 50 2-dose participants were enrolled.
Results for both studies showed that the novel OPV2 candidates were safe and well-tolerated, with similar immunogenicity to monovalent OPV2 despite high baseline immunity. In adults, young children, and infants, adverse reactions to the vaccines were mild and similar across vaccine groups.
In adults, the most frequent adverse events were headache, fatigue, abdominal pain, diarrhea, and myalgia. Of the 4 serious adverse events, which mainly consisted of gastrointestinal disorders, only 1 was possibly related to the OPV2-c2 vaccine.
In children and infants, the most frequent adverse events were mild or moderate and consisted of abnormal crying, irritability, transient loss of appetite, vomiting, and fever. Three children had serious adverse events leading to hospitalization, but none were considered to be causally associated with vaccination.
In adults, the seroprotection rate was 100% after first dose (day 28) and second dose (day 56) of either novel OPV2 candidate compared with 97% and 98% for 1 or 2 doses of monovalent OPV2, respectively. In IPV-vaccinated adults, 89% (42/47) were seropositive at baseline and this increased to 100% in both novel OPV2 groups after the first dose.
Given their immunization history, children had high baseline seroprotection rates against type 2 poliovirus: 100% in the monovalent OPV2 group, 100% in the OPV2-c1 group, and 94% in the OPV2-c2 group. Although seroconversion rates were higher after novel OPV2 candidates than after monovalent OPV2, the many confounding factors included the “number, type, and time since last type 2 vaccination, and possible environmental exposure of monovalent OPV2 vaccinees to type 2 vaccine before type 2 OPV withdrawal,” the researchers noted.2
In infants, the noninferiority criterion was met for both the low-dose and high-dose novel OPV2-c1 (-0.7%; 95% CI, -7.4 -6.7 and -0.1%; 95% CI, -6.4-7.2, respectively). While noninferiority was also achieved for the high-dose novel OPV2-c2 (-0.7%; 95% CI, -5.3-7.9), this was not true for the low-dose novel OPV2-c2 (-3.3%; 95% CI, -10.6-4.5).
While further study is underway, initial analyses of stool viral shedding rates suggest that the novel OPV2 candidates have a higher genetic stability than the monovalent OPV2.
Limitations included the necessity to do 2 separate studies, small number of trial participants, and the inability to compare immunogenicity and viral shedding in children aged 1 to 5 years.
Together with manufacturing and epidemiological considerations, findings from both studies “contributed to selection of novel OPV2-c1 as the first new vaccine to be listed under the [World Health Organization] Emergency Use Listing procedure for use in type 2 circulating vaccine-derived poliovirus outbreaks,” Sáez-Llorens et al concluded.2
Disclosure: One study author in each study declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
1. De Coster I, Leroux-Roels I, Bandyopadhyay AS, et al. Safety and immunogenicity of two novel type 2 oral poliovirus vaccine candidates compared with a monovalent type 2 oral poliovirus vaccine in healthy adults: two clinical trials. Lancet. 2021;397(10268):39-50. doi:10.1016/S0140-6736(20)32541-1
2. Sáez-Llorens X, Bandyopadhyay AS, Gast C, et al. Safety and immunogenicity of two novel type 2 oral poliovirus vaccine candidates compared with a monovalent type 2 oral poliovirus vaccine in children and infants: two clinical trials. Lancet. 2021;397(10268):27-38. doi:10.1016/S0140-6736(20)32540-X