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A new EV71 VP3 epitope in norovirus P particle vector displays neutralizing activity and protection in vivo in mice
Institution: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. 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. Laboratory of Microbiology, College of Pharmacy, Ajou University, Suwon 443-749, Republic of Korea;2. Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon 200-701, Republic of Korea;3. Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Republic of Korea;4. Department of Microbiology, Chungcheongnam-Do Institute of Health and Environment Research, Daejeon 300-801, Republic of Korea;5. Division of Vaccine Research, Center for Infectious Diseases, National Institute of Health, Korea Centers for Diseases Control and Prevention, Cheongju 361-951, Republic of Korea;6. Mucosal Immunology Laboratory, Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea;1. National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China;2. Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, 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. Hualan Biological Bacterin Company, Xinxiang 453003, Henan, China
Abstract:Enterovirus 71 (EV71) and Coxsackievirus A16 (CVA16), as the main agents causing hand, foot and mouth disease (HFMD), have become a serious public health concern in the Asia-Pacific region. Recently, various neutralizing B cell epitopes of EV71 were identified as targets for promising vaccine candidates. Structural studies of Picornaviridae indicated that potent immunodominant epitopes typically lie in the hypervariable loop of capsid surfaces. However, cross-neutralizing antibodies and cross-protection between EV71 and CVA16 have not been observed. Therefore, we speculated that divergent sequences of the two viruses are key epitopes for inducing protective neutralizing responses. In this study, we selected 10 divergent epitope candidates based on alignment of the EV71 and CVA16 P1 amino acid sequences using the Multalin interface page, and these epitopes are conserved among all subgenotypes of EV71. Simultaneously, by utilizing the norovirus P particle as a novel vaccine delivery carrier, we identified the 71-6 epitope (amino acid 176–190 of VP3) as a conformational neutralizing epitope against EV71 in an in vitro micro-neutralization assay as well as an in vivo protection assay in mice. Altogether, these results indicated that the incorporation of the 71-6 epitope into the norovirus P domain can provide a promising candidate for an effective synthetic peptide-based vaccine against EV71.
Keywords:Enterovirus 71  Norovirus P particle  Neutralizing antibody  Epitope  Antigen presentation
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