Efficacy, Safety, and Immunogenicity of an Enterovirus 71 Vaccine in China

BackgroundEnterovirus 71 (EV71) is one of the major causative agents of outbreaks of hand, foot, and mouth disease or herpangina worldwide. This phase 3 trial was designed to evaluate the efficacy, safety, and immunogenicity of an EV71 vaccine. MethodsWe conducted a randomized, double-blind, placebo-controlled, multicenter trial in which 10,007 healthy infants and young children (6 to 35 months of age) were randomly assigned in a 1:1 ratio to receive two intramuscular doses of either EV71 vaccine or placebo, 28 days apart. The surveillance period was 12 months. The primary end point was the occurrence of EV71-associated hand, foot, and mouth disease or herpangina. ResultsDuring the 12-month surveillance period, EV71-associated disease was identified in 0.3% of vaccine recipients (13 of 5041 children) and 2.1% of placebo recipients (106 of 5028 children) in the intention-to-treat cohort. The vaccine efficacy against EV71-associated hand, foot, and mouth disease or herpangina was 94.8% (95% confidence interval [CI], 87.2 to 97.9; P<0.001) in this cohort. Vaccine efficacies against EV71-associated hospitalization (0 cases vs. 24 cases) and hand, foot, and mouth disease with neurologic complications (0 cases vs. 8 cases) were both 100% (95% CI, 83.7 to 100 and 42.6 to 100, respectively). Serious adverse events occurred in 111 of 5044 children in the vaccine group (2.2%) and 131 of 5033 children in the placebo group (2.6%). In the immunogenicity subgroup (1291 children), an anti-EV71 immune response was elicited by the two-dose vaccine series in 98.8% of participants at day 56. An anti-EV71 neutralizing antibody titer of 1:16 was associated with protection against EV71-associated hand, foot, and mouth disease or herpangina. ConclusionsThe EV71 vaccine provided protection against EV71-associated hand, foot, and mouth disease or herpangina in infants and young children. (Funded by Sinovac Biotech; ClinicalTrials.gov number, NCT01507857.) Enterovirus 71 (EV71) is an important cause of hand, foot, and mouth disease, especially in China. In this phase 3 trial involving 10,077 infants and children in China, an EV71 vaccine provided protection against EV71-associated disease. Enterovirus 71 (EV71), an enterovirus that is not associated with poliomyelitis, was one of the major causative agents of outbreaks of hand, foot, and mouth disease or herpangina in Europe,(1)-(3) Australia,(4),(5) and Japan(6),(7) between 1972 and 1988, and it has been implicated in a series of outbreaks across the Asia-Pacific region since the 1990s.(8)-(11) The largest Asia-Pacific epidemic occurred in China in 2008, when approximately 490,000 infections and 126 deaths in infants and young children were reported.(12) The vast majority of severe cases and fatal cases occurred in children younger than 3 years of age. EV71 ...