Immunogenicity, safety, cross-reaction, and immune persistence of an inactivated enterovirus A71 vaccine in children aged from two months to 11 years in Taiwan

Background: To fight against enterovirus A71 (EV-A71)-associated diseases, vaccine development was initiated in Taiwan focusing on two-month-old infants. Methods: We conducted a phase II, double-blind, randomised, placebo-controlled study on infants and children aged two months to 11 years. This study was conducted in 4 parts (2a, 2b, 2c, and 2d) with age de-escalation sequentially. Two doses were administered with a 28-day or 56-day interval. Participants aged two months to <two years received a booster dose at one year after the first dose. During the surveillance period, solicited adverse events (AEs) and unsolicited AEs were recorded for safety evaluation. Blood samples were collected for neutralising antibody assay at various times. Immune persistence and booster effects were also assessed. Results: A total of 363 children completed the study. Most AEs were mild and unrelated to treatment. No vaccine-related serious adverse events (SAEs) were reported. Geometric mean titres (GMTs) of serum neutralising antibody titres increased profoundly. Most participants in the vaccine groups achieved defined seroprotection (neutralization titre ≥ 1:32) after the second vaccination and persisted for two years. Furthermore, the EV-A71 vaccine could provide a cross-reaction against other EV-A71 strain genotypes: B5, C4a, C4b, and C5. Conclusions: The mid dose of the EV-A71 vaccine elicited high immune response and were tolerable in participants aged between two months and 11 years in all dosing groups.