The Immunogenicity, Safety And Protective Efficacy Of Enterovirus 71 Vaccine In Children Aged 3-5 Years

【Background】Hand,foot,and mouth disease(HFMD)is a common infectious disease mainly in the children under 5 years of age.Although most of the HFMD cases were mild or moderate,some severe HFMD cases can progress rapidly and lead to fatal cardiopulmonary and neurologic complications,especially the cases associated with EV71(Enterovirus 71,EV71).In recent decades,EV71-associated HFMD cases,particularly severe and fatal HFMD cases becoming a serious public health threat and economic burden in the china.It is worth nothing that children aged 3–5 years accounted for approximately 30% of HFMD cases 【Methods】A randomized,double-blind,placebo-controlled,batch-to-batch consistency clinical trial enrolling 1400 participants aged 6–59 months was performed.We pooled the participants receiving three batches of EV71 vaccine together based on the original study and then stratified them into the 6–35 months and 3–5 years and then analyze of the immunogenicity,safety and predicted vaccine efficacy of EV71 vaccine in children aged 3–5 years.The primary end point of this post-hoc study was the non-inferiority analysis of the geometric mean titer of anti-EV71 neutralizing antibody in children aged 3–5 years.【Result】In the vaccine group,the GMT of anti-EV71 neutralizing antibody titers in 242 children aged 3–5 years on day 56 was 132.7(95% CI,110.3–159.6),which was noninferior to that generated in 717 infants aged 6–35 months with a GMT of 84.4(95% CI,77.8–91.5).During the 56-day follow-up period,the incidence of the injection-site or systemic adverse reactions was less frequent in children aged 3–5 years(47.0%)than that in infants aged 6–35 months(60.1%)(P=0.0026).The predicted vaccine efficacy in children aged 3–5 years were 94.7% and 85.1% respectively by the step function and continuous logistic function.【Conclusion】The EV71 vaccine was highly immunogenic,satisfactory safe and acceptable predicted efficacy when administered to children aged 3–5 years.