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A novel inactivated enterovirus 71 vaccine can elicit cross-protective immunity against coxsackievirus A16 in mice
Institution:1. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science & School of Public Health, Xiamen University, Xiamen, China;2. Department of Obstetrics and Gynecology, Affiliated Zhongshan Hospital, Xiamen University, Xiamen, China;1. Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan 650118, China;2. Jiangsu Convac Biotechnology Co., Ltd., Taizhou, Jiangsu 225300, China;1. Vaccine Research Center, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China;2. National Center for Protein Science ? Shanghai, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201210, China;1. School of Life Sciences, Jilin University, Changchun, PR China;2. National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun, PR China;3. Key Laboratory for Molecular Enzymology & Engineering, The Ministry of Education, Jilin University, Changchun, PR China;4. Harbin Center for Disease Control and Prevention, Harbin 150056, PR China;5. State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, PR China;1. National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan;2. Institute of Oral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan;3. Graduate Institute of Immunology, China Medical University, Taichung, Taiwan;4. Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan;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
Abstract:Hand, foot, and mouth disease (HFMD) is a highly contagious disease that mainly affects infants and children. Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the major pathogens of HFMD. Two EV71 vaccines were recently licensed in China and the administration of the EV71 vaccines is believed to significantly reduce the number of HFMD-related severe or fatal cases. However, a monovalent EV71 vaccine cannot cross-protect against CA16 infection, this may result in that it cannot effectively control the overall HFMD epidemic. In this study, a chimeric EV71, whose VP1/210–225 epitope was replaced by that of CA16, was constructed using a reverse genetics technique to produce a candidate EV71/CA16 bivalent vaccine strain. The chimeric EV71 was infectious and showed similar growth characteristics as its parental strain. The replacement of the VP1/210–225 epitope did not significantly affect the antigenicity and immunogenicity of EV71. More importantly, the chimeric EV71 could induce protective immunity against both EV71 and CA16, and protect neonatal mice against either EV71 or CA16 lethal infections, the chimeric EV71 constructed in this study was shown to be a feasible and promising candidate bivalent vaccine against both EV71 and CA16. The construction of a chimeric enterovirus also provides an alternative platform for broad-spectrum HFMD vaccines development.
Keywords:Enterovirus 71  Coxsackievirus A16  Vaccine  Chimeric virus  Neutralizing epitope
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