An Inactivated Enterovirus 71 Vaccine in Healthy Children

BackgroundEnterovirus 71 (EV71) is a major cause of hand, foot, and mouth disease in children and may be fatal. A vaccine against EV71 is needed. MethodsWe conducted a randomized, double-blind, placebo-controlled phase 3 trial involving healthy children 6 to 71 months of age in Guangxi Zhuang Autonomous Region, China. Two doses of an inactivated EV71 vaccine or placebo were administered intramuscularly, with a 4-week interval between doses, and children were monitored for up to 11 months. The primary end point was protection against hand, foot, and mouth disease caused by EV71. ResultsA total of 12,000 children were randomly assigned to receive vaccine or placebo. Serum neutralizing antibodies were assessed in 549 children who received the vaccine. The seroconversion rate was 100% 4 weeks after the two vaccinations, with a geometric mean titer of 170.6. Over the course of two epidemic seasons, the vaccine efficacy was 97.4% (95% confidence interval [CI], 92.9 to 99.0) according to the intention-to-treat analysis and 97.3% (95% CI, 92.6 to 99.0) according to the per-protocol analysis. Adverse events, such as fever (which occurred in 41.6% of the participants who received vaccine vs. 35.2% of those who received placebo), were significantly more common in the week after vaccination among children who received the vaccine than among those who received placebo. ConclusionsThe inactivated EV71 vaccine elicited EV71-specific immune responses and protection against EV71-associated hand, foot, and mouth disease. (Funded by the National Basic Research Program and others; ClinicalTrials.gov number, NCT01569581.) Enterovirus 71 (EV71), a cause of hand, foot, and mouth disease, may be associated with poliomyelitis-like paralysis. In this report from China, a vaccine was shown to significantly decrease EV71-associated illness in children. Epidemics of hand, foot, and mouth disease in children have emerged recently in Asia and have been caused primarily by enterovirus 71 (EV71) and coxsackievirus A16,(1) which typically show two peak epidemic incidences each year, in May and October.(2)-(5) An important clinical concern regarding hand, foot, and mouth disease is central nervous system injury, which occurs during the disease course in some severe cases and may result in a poor outcome.(6)-(11) Infection with the EV71 C4 genotype accounts for 40.1 to 55.4% of cases of hand, foot, and mouth disease, with considerable associated mortality, including thousands of deaths ...