title: Review of enterovirus 71 vaccines.
abstract: 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.
authors.affiliation: Vaccine Research and Development Center, National Health Research Institutes, Zhunan Town Graduate Institute of Immunology, China Medical University, Taichung, Taiwan.
authors.forename: Pele
authors.initials: P
authors.lastname: Chong
authors.affiliation: Vaccine Research and Development Center, National Health Research Institutes, Zhunan Town.
authors.forename: Chia-Chyi
authors.initials: CC
authors.lastname: Liu
authors.affiliation: Vaccine Research and Development Center, National Health Research Institutes, Zhunan Town Graduate Institute of Immunology, China Medical University, Taichung, Taiwan.
authors.forename: Yen-Hung
authors.initials: YH
authors.lastname: Chow
authors.affiliation: Vaccine Research and Development Center, National Health Research Institutes, Zhunan Town.
authors.forename: Ai-Hsiang
authors.initials: AH
authors.lastname: Chou
authors.affiliation: VaxiBio Inc, Toronto, Ontario, Canada.
authors.forename: Michel
authors.initials: M
authors.lastname: Klein
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D000940:Antigenic Variation; D017326:Clinical Trials, Phase III as Topic; D056738:Cross Protection; D004195:Disease Models, Animal; D029821:Enterovirus A, Human / Q000276:immunology*; D006232:Hand, Foot and Mouth Disease / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology*; D006801:Humans; D016896:Treatment Outcome; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000276:immunology* / Q000302:isolation & purification
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D014765:Viral Vaccines
keywords: enterovirus 71; hand, foot and mouth disease; human enterovirus A (HEV-A); inactivated whole virion vaccine; waning immunity