A randomised trial of a bioreactor-produced EV-A71 vaccine for endemic control in children.

Enterovirus (EV) A71 causes endemic outbreaks of hand-foot-mouth disease (HFMD) and herpangina in young children, occasionally leading to severe complications and fatal outcomes. We evaluated EnVAX-A71, a bioreactor-produced, aluminum-adjuvanted inactivated EV-A71 (B4/E59) vaccine, in a randomized, double-blind, placebo-controlled phase 3 trial in Taiwan and Vietnam. A total of 4011 children aged 2-71 months were randomized 3:2 to vaccine or placebo; the primary endpoint was laboratory-confirmed EV-A71-associated HFMD/herpangina, evaluated from 28 days after dose two over a follow-up of 1 to 2 years (median, 490 days). In the primary analysis (n = 3733), one case occurred in vaccine recipients versus 70 in placebo (0.3 vs 39.2 per 1000 person-years), yielding 99.2% vaccine efficacy (95% CI: 94.3-99.9, p < 0.001). Seroprotection (neutralizing antibody titer ≥1:32) reached 98.7% at day 56 and remained ≥98% through one year. No vaccine-group hospitalizations occurred versus 19 in placebo (100% efficacy, 95% CI: 90.6-100.0). Safety profiles were comparable between groups. These findings support EnVAX-A71 for endemic EV-A71 control (ClinicalTrials.gov NCT05099029).