The aluminum phosphate-adjuvanted inactivated enterovirus 71 (EV71) vaccine was highly effective for the prevention of EV71-associated infections among infants and children. These findings, from a phase 3 trial, were published in The Lancet.
This prospective, randomized, multicenter study was conducted in Taiwan and Vietnam in 2019. Children (N=3049) aged between 2 and 71 months were randomly assigned in a 1:1 fashion to receive either 2 intramuscular injections of the EV71 vaccine (n=1521) or placebo (n=1528). Patients assigned to the vaccine group received the first dose at enrollment and the second dose after 56 days (both 0.5 mL), and those aged between 2 and 23 months received a third dose on day 366. The vaccine comprised an inactivated whole EV71 B4 genotype virus particle with 2.5 µg of EV71 protein. Safety and efficacy were evaluated.
Among patients included in the primary efficacy analysis (n=2959), 1476 were in the vaccine group and 1483 were in the placebo group. There were 22 cases of EV71 infection diagnosed among patients included in this analysis, all of which occurred among those in the placebo group (incidence rate, 11.15 per 1000 patient-years; 95% CI, 7.34-16.94).
Among patients in the vaccine group, the efficacy of the EV71 vaccine was 100%, with an efficacy of 96.8% (95% CI, 85.5-100; P <.0001) observed after adjustment via Poisson regression.
After stratification by age group, the researchers found that 59% of EV71 infection diagnoses occurred among patients between 6 and 23 months, 23% were among those between 2 and 5 months, and 18% were among those between 24 and 71 months.
All but 1 positive case of EV71 infection occurred among patients from Vietnam, 11 of whom were infected with the B5 genotype and 10 with the C4 genotype. The single case detected among a patient from Taiwan could not be genotyped.
In the immunogenicity substudy, the seroprotection rates of the EV71 vaccine were 99.5% on day 85, 97.9% on day 366, and 100% on day 394, surpassing the planned primary (90%) and secondary (70%) seroprotection efficacy endpoints. For the placebo group, seroprotection remained below 15.6% at all timepoints.
The occurrence of adverse events was similar between patients in the vaccine vs placebo groups (56.9% vs 55.8%). Among patients in the vaccine group, the most common events included injection site pain (23.3%), fever (23.1%), fussiness (20.4%), decreased appetite (18.9%), swelling (12.1%), diarrhea (11.7%), erythema (11.2%), and nausea/vomiting (10.0%). Similar results were observed among patients in the placebo group. The rate of unsolicited adverse events also was similar between the vaccine and placebo groups (64.2% vs 62.6%).
This study was limited as the patients were not evaluated for asymptomatic infection.
“If approved, [this] will be the first EV71 vaccine ready for distribution worldwide,” the researchers noted.
Disclosure: Multiple authors declared affiliations with industry. Please see the original reference for a full list of disclosures.
Nguyen TT, Chiu C-H, Lin C-Y et al. Efficacy, safety, and immunogenicity of an inactivated, adjuvanted enterovirus 71 vaccine in infants and children: a multiregion, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet. 2022;399(10336):1708-1717. doi:10.1016/S0140-6736(22)00313-0