An inactivated enterovirus 71 vaccine in healthy children

N Engl J Med. 2014 Feb 27;370(9):829-37. doi: 10.1056/NEJMoa1303224.

Abstract

Background: Enterovirus 71 (EV71) is a major cause of hand, foot, and mouth disease in children and may be fatal. A vaccine against EV71 is needed.

Methods: We 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.

Results: A 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.

Conclusions: The 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.).

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Child, Preschool
  • China
  • Double-Blind Method
  • Enterovirus A, Human / genetics
  • Enterovirus A, Human / immunology*
  • Female
  • Fever / etiology
  • Hand, Foot and Mouth Disease / epidemiology
  • Hand, Foot and Mouth Disease / immunology
  • Hand, Foot and Mouth Disease / prevention & control*
  • Humans
  • Infant
  • Injections, Intramuscular
  • Kaplan-Meier Estimate
  • Male
  • Vaccines, Inactivated
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / adverse effects
  • Viral Vaccines / immunology*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Vaccines, Inactivated
  • Viral Vaccines

Associated data

  • ClinicalTrials.gov/NCT01569581