Research in context
Evidence before this study
In the Asia-Pacific region, enterovirus 71 (EV71) poses prevalent and recurring threats that affect children the most. Serious EV71 infections in children lead to neurological complications or death. Currently, however, only three formalin-inactivated, C4 genotype-based EV71 vaccines have been approved for use in China, leaving children from other regions vulnerable. On Nov 19, 2021, we searched PubMed for published clinical trials that assessed the safety and efficacy of EV71 vaccines with no language restrictions. Using key terms such as “enterovirus 71”, “clinical trials”, “efficacy”, and “vaccine”, we found 14 publications, eight of which reported results for clinical or randomised controlled trials. All eight publications pertained to the three aforementioned vaccines, and the trials were all done in China. Even though these three vaccines are highly effective against EV71 infections of the C4 genotype, they have only been approved for children older than 6 months. Introducing a vaccine that casts a wider net of protection to include younger infants from other countries against different genotypes is, therefore, imperative.
Added value of this study
EV71vac is a formalin-inactivated, B4 genotype-based EV71 vaccine. We enrolled over 3000 young children aged 2 months to 5 years from Taiwan and Vietnam. Participants received two doses of EV71vac 57 days apart, and those aged 2 months to 1 year received a third booster shot a year after their first dose. By December, 2019, all participants had received their second dose, and by April, 2021, we had 22 confirmed cases of EV71-associated diseases, which formed the basis of our efficacy analysis. All 22 confirmed cases occurred in the placebo group and were caused by B5 and C4 genotypes. The lack of confirmed cases in the vaccine group gives EV71vac the calculated efficacy of 100%, and shows EV71vac's capacity to cross-protect against B5 and C4 genotypes.
Implications of all the available evidence
In our phase 2 trial, EV71vac was shown to be safe and immunogenic. In this phase 3 trial, EV71vac proves it is safe and highly effective against EV71 associated diseases in children as young as 2 months to 5 years of age, and offers cross-protection against B4 and C4 genotypes. EV71vac is manufactured in compliance with the Pharmaceutical Inspection Co-operation Scheme, and if approved by regulatory authority, will be the first EV71 vaccine ready for distribution worldwide.