4.5 Review

Prospect and challenges for the development of multivalent vaccines against hand, foot and mouth diseases

Journal

VACCINE
Volume 32, Issue 47, Pages 6177-6182

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2014.08.064

Keywords

Human enterovirus A (HEV-A); Hand, foot and mouth diseases; Enterovirus 71; Coxsackievirus, Inactivated whole virion vaccine; Serum-free culture technology; Cross-neutralizing antibody; Immunodominant epitopes; Waning immunity

Funding

  1. National Science Council (NSC) of Taiwan [98A1-VCSP01-014]

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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. (C) 2014 Elsevier Ltd. All rights reserved.

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