Researchers found that two novel type 2 oral poliovirus (OPV2) candidate vaccines—OPV2-c1 and OPV2-c2—are safe, well-tolerated, and effective in children and infants, as well as adults, and may be an important addition to the existing armamentarium against poliovirus, according to two studies published in The Lancet.
“Continued emergence and spread of circulating vaccine-derived type 2 polioviruses and vaccine-associated paralytic poliomyelitis from Sabin OPVs has stimulated development of two novel type 2 OPV candidates (OPV2-c1 and OPV2-c2) designed to have similar immunogenicity, improved genetic stability, and less potential to reacquire neurovirulence. We aimed to assess safety and immunogenicity of the two novel OPV candidates compared with a monovalent Sabin OPV in children and infants,” wrote researchers of the first study, led by Xavier Sáez-Llorens, MD, of the Hospital del Niño Dr José Renán Esquivel, Panama City, Panama.
These new vaccines were engineered in response to a declaration from the World Health Organization that type 2 circulating vaccine-derived poliovirus outbreaks are a Public Health Emergency of International Concern, and as part of the Global Polio Eradication Initiative response strategy.
Sáez-Llorens and colleagues conducted two single-center, multi-site, partly masked, randomized trials in healthy children aged 1-4 years and infants aged 18-22 weeks in Panama. The first was a control, phase 4 study with monovalent Sabin OPV2, and the second, a phase 2 study with low- and high-dose novel OPV2 candidates. In all, 150 children and 684 infants were included. All were administered one OPV2 vaccination, and subsets received two doses 28 days apart.
After 28 days and one dose, the seroprotection rate in children was 100% for monovalent OPV2 and both novel OPV2 candidates. At the same time point in infants, seroprotection rates were as follows:
- 94% (91 of 97; 95% CI: 87-98) with the monovalent OPV2 vaccine.
- 94% (134 of 143; 95% CI: 88-97) with the high-dose novel OPV2-c1 vaccine.
- 93% (122 of 131; 95% CI: 87-97) with the low-dose novel OPV2-c1 vaccine.
- 95% (138 of 146; 95% CI: 90-98) with the high-dose novel OPV2-c2 vaccination.
- 91% (115 of 127; 95% CI: 84-95) with the low-dose novel OPV2-c2 vaccination.
In the high-dose novel OPV2-c1 group, the conversion rate was 98% (95% CI: 89–100), and in the high-dose novel OPV2-c2 group, 100% (95% CI: 93–100). Seroconversion in the low-dose novel OPV2 groups, with 10-fold less virus, was 98% (95% CI: 88–100) for novel OPV2-c1, and 86% (95% CI: 73–95) for novel OPV2-c2.
Both the low- and high-dose novel OPV2-c1 and high-dose novel OPV2-c2 were shown to be non-inferior, despite recipients of the monovalent OPV2 having higher baseline immunity.
“As expected, given their immunization history, children had high baseline seroprotection rates against type 2 poliovirus: 100% in the historical control monovalent OPV2 group, and 100% in the novel OPV2-c1 group and 94% in the novel OPV2-c2 group,” noted researchers.
Vaccinations were safe and well tolerated, with no serious adverse or medical events occurred. Adverse events primarily included transient appetite loss, abnormal crying, irritability, and fever, and most were mild.
“These two separate studies in previously vaccinated children and in infants provide support for the safety and acceptable tolerability of low and high doses of two novel OPV2 candidates, similar to the licensed monovalent OPV2 vaccine in infants, and of high doses in young children. All vaccines displayed acceptable reactogenicity profiles with mainly mild and transient systemic adverse events. Serious or severe adverse events were infrequent and not considered causally associated with vaccination,” concluded Sáez-Llorens et al.
Limitations of this study include need to establish control data in children and infants who received monovalent OPV2 before its global withdrawal in 2016, and the inability to compare immunogenicity and viral shedding in children aged 1-5 years.
In the second study, conducted by researchers in Antwerp led by Ilse De Coster, MD, of the University of Antwerp, Wilrijk, Belgium, compiled results from two randomized trials: a phase 4 historical control trial of monovalent OPV2 and a phase 2 trial with novel OPV2-c1 and novel OPV2-c2 vaccine candidates in healthy adults who had at least three polio vaccines.
In the historical control trial, researchers included 100 volunteers randomized to either one or two doses of monovalent OPV2. In the novel OPV2 phase 2 trial, 200 volunteers who had received at least three OPVs were randomized to either one or two doses of novel OPV2-c1 or to one or two doses of novel OPV2-c2. An additional 50 participants previously vaccinated with IPV were randomized to either novel OPV2-c1, novel OPV2-c2, or placebo.
De Coster and colleagues found that these novel OPV2 candidate vaccines were as safe, well tolerated, and as immunogenic as monovalent OPV2 in adults previously vaccinated with OPV and IPV. All vaccines were safe, with no vaccine-related withdrawals or serious adverse events.
After the first vaccine dose in the previously OPV-vaccinated participants, systemic adverse events occurred in 62% of the monovalent OPV2 recipients, in 71% of the novel OPV2-c1 recipients, and in 74% of the novel OPV2-c vaccine. The corresponding number of events classified as severe were four, three, and two, respectively. The most frequent adverse events were headache, fatigue, abdominal pain, diarrhea, and myalgia.
In IPV-vaccinated participants, adverse events occurred in 94%, 81%, and 88%, respectively. One severe reaction occurred in those receiving novel OPV2-c2 vaccination and two in those in the placebo group. Severe adverse events mainly consisted of gastrointestinal disorders, the study authors explained — diarrhea, nausea, and abdominal pain.
Among OPV-vaccinated participants, of whom 97% were seropositive at baseline, 100% of those receiving the novel OPV2 vaccine and 97% of those vaccinated with the monovalent OPV2 vaccines were seropositive.
“Novel OPV2 candidates were as safe, well tolerated, and immunogenic as monovalent OPV2 in previously OPV-vaccinated and IPV-vaccinated adults. These data supported the further assessment of the vaccine candidates in children and infants,” concluded De Coster and fellow researchers.
Study limitations included the need to perform two separate trials and the inclusion of fully vaccinated adults.
In an accompanying editorial, Kimberly M. Thompson, ScD, of Kid Risk, Inc., Orlando, wrote: “Both studies used the best possible methods to compare novel and monovalent OPV2 given global OPV2 containment constraints. Both are limited by the small numbers of trial participants (e.g., observations of reversion and rare events like vaccine-associated paralytic polio would require use in millions of people, similar to OPV5), different participant immunity profiles, and the potential for secondary monovalent OPV2 exposure for the historical controls but not the novel OPV2 trials. The results from these two studies and the Emergency Use Listing represent exciting next steps for a world that already needed more OPV2 before the Covid-19 pandemic. This progress will allow for broader use of novel OPV2 and the observation of evidence related to its actual performance in the field.”
She concluded that these two studies “represent promising next steps towards the future of global poliovirus control and eradication using better performing OPV strains.”
Two novel type 2 OPV candidates (OPV2-c1 and OPV2-c2) have been designed to have similar immunogenicity, improved genetic stability, and less potential to reacquire neurovirulence, and are safe, well-tolerated, and effective in children, infants, and adults.
Two new poliovirus vaccine candidates have been developed as a response to a WHO declaration that type 2 circulating vaccine-derived poliovirus outbreaks are a public health emergency.
E.C. Meszaros, Contributing Writer, BreakingMED™
Sáez-Llorens, De Coster, and Thompson reported no disclosures.
The study from De Coster and colleagues was funded by the University of Antwerp and the Bill & Melinda Gates Foundation.
Cat ID: 125
Topic ID: 79,125,125,190,31,44,561,151,925