title: Prospect and challenges for the development of multivalent vaccines against hand, foot and mouth diseases.
abstract: Enterovirus 71 (EV71), an emerging neurotropic virus and coxsackieviruses (CV) are the major causative agents of hand, foot and mouth diseases (HFMD). These viruses have become a serious public health threat in the Asia Pacific region. Formalin-inactivated EV71 (FI-EV71) vaccines have been developed, evaluated in human clinical trials and were found to elicit full protection against EV71. Their failure to prevent CVA16 infections could compromise the acceptability of monovalent EV71 vaccines. Bivalent FI-EV71/FI-CVA16 vaccines have been found to elicit strong neutralizing antibody responses against both viruses in animal models but did not protect against CVA6 and CVA10 viral infections in cell culture neutralization assay. In this review, we discuss the critical bottlenecks in the development of multivalent HFMD vaccines, including the selection of vaccine strains, animal models to assess vaccine potency, the definition of end-points for efficacy trials, and the need for improved manufacturing processes to produce affordable vaccines.
authors.affiliation: Vaccine R&D Center, National Health Research Institutes, Zhunan Town 350, Miaoli County, Taiwan.
authors.forename: Chia-Chyi
authors.initials: CC
authors.lastname: Liu
authors.affiliation: Vaccine R&D Center, National Health Research Institutes, Zhunan Town 350, Miaoli County, Taiwan.
authors.forename: Yen-Hung
authors.initials: YH
authors.lastname: Chow
authors.affiliation: Vaccine R&D Center, National Health Research Institutes, Zhunan Town 350, Miaoli County, Taiwan; Graduate Institute of Immunology, China Medical University, Taichung, Taiwan. Electronic address: pelechong@nhri.org.tw.
authors.forename: Pele
authors.initials: P
authors.lastname: Chong
authors.affiliation: VaxiBio Inc., Toronto, ON, Canada. Electronic address: michel.klein@umontreal.ca.
authors.forename: Michel
authors.initials: M
authors.lastname: Klein
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D001208:Asia; D002986:Clinical Trials as Topic; D056738:Cross Protection; D004770:Enterovirus; D029821:Enterovirus A, Human; D004769:Enterovirus Infections / Q000517:prevention & control*; D006232:Hand, Foot and Mouth Disease / Q000517:prevention & control*; D006801:Humans; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D015164:Vaccines, Inactivated / Q000276:immunology / Q000627:therapeutic use; D014765:Viral Vaccines / Q000276:immunology* / Q000627:therapeutic use
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015164:Vaccines, Inactivated; D014765:Viral Vaccines
keywords: Coxsackievirus, Inactivated whole virion vaccine; Cross-neutralizing antibody; Enterovirus 71; Hand, foot and mouth diseases; Human enterovirus A (HEV-A); Immunodominant epitopes; Serum-free culture technology; Waning immunity