Prospect and challenges for the development of multivalent vaccines against hand,foot and mouth diseases |
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Authors: | Chia-Chyi Liu Yen-Hung Chow Pele Chong Michel Klein |
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Institution: | 1. Vaccine R&D Center, National Health Research Institutes, Zhunan Town 350, Miaoli County, Taiwan;2. Graduate Institute of Immunology, China Medical University, Taichung, Taiwan;3. VaxiBio Inc., Toronto, ON, Canada |
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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. |
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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 |
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