Review of enterovirus 71 vaccines

Clin Infect Dis. 2015 Mar 1;60(5):797-803. doi: 10.1093/cid/ciu852. Epub 2014 Oct 28.


Enterovirus 71 (EV71) and coxsackieviruses are the major causative agents of hand, foot, and mouth disease (HFMD) outbreaks worldwide and have a significant socioeconomic impact, particularly in Asia. Formalin-inactivated (FI) EV71 vaccines evaluated in human clinical trials in China, Taiwan, and Singapore were found to be safe and to elicit strong neutralizing antibody responses against EV71 currently circulating in Asia. The results from 3 different phase 3 clinical trials performed in young children (6-60 months) indicate that the efficacy of FI-EV71 vaccines is >90% against EV71-related HFMDs and >80% against EV71-associated serious diseases, but the vaccines did not protect against coxsackievirus A16 infections. Here we discuss the critical factors affecting EV71 vaccine product registration, including clinical epidemiology, antigenic shift issues in cross-protection and vaccine strain selection, standardized animal models for potency testing, and cost-effective manufacturing processes for potential incorporation of FI-EV71 vaccine into Expanded Programme on Immunization vaccines.

Keywords: enterovirus 71; hand, foot and mouth disease; human enterovirus A (HEV-A); inactivated whole virion vaccine; waning immunity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Antigenic Variation
  • Clinical Trials, Phase III as Topic
  • Cross Protection
  • Disease Models, Animal
  • Enterovirus A, Human / immunology*
  • Hand, Foot and Mouth Disease / epidemiology
  • Hand, Foot and Mouth Disease / prevention & control*
  • Hand, Foot and Mouth Disease / virology*
  • Humans
  • Treatment Outcome
  • Viral Vaccines / administration & dosage*
  • Viral Vaccines / immunology*
  • Viral Vaccines / isolation & purification


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Viral Vaccines