title: A new EV71 VP3 epitope in norovirus P particle vector displays neutralizing activity and protection in vivo in mice.
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.
authors.affiliation: School of Life Sciences, Jilin University, Changchun, PR China; National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun, PR China.
authors.forename: Liping
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Harbin Center for Disease Control and Prevention, Harbin 150056, PR China.
authors.forename: Rongjun
authors.initials: R
authors.lastname: Fan
authors.affiliation: School of Life Sciences, Jilin University, Changchun, PR China; National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun, PR China.
authors.forename: Shiyang
authors.initials: S
authors.lastname: Sun
authors.affiliation: School of Life Sciences, Jilin University, Changchun, PR China; National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun, PR China.
authors.forename: Peihu
authors.initials: P
authors.lastname: Fan
authors.affiliation: School of Life Sciences, Jilin University, Changchun, PR China; National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun, PR China; Key Laboratory for Molecular Enzymology & Engineering, The Ministry of Education, Jilin University, Changchun, PR China; State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, PR China.
authors.forename: Weiheng
authors.initials: W
authors.lastname: Su
authors.affiliation: School of Life Sciences, Jilin University, Changchun, PR China; National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun, PR China; Key Laboratory for Molecular Enzymology & Engineering, The Ministry of Education, Jilin University, Changchun, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: School of Life Sciences, Jilin University, Changchun, PR China; National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun, PR China; Key Laboratory for Molecular Enzymology & Engineering, The Ministry of Education, Jilin University, Changchun, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: School of Life Sciences, Jilin University, Changchun, PR China; National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun, PR China; Key Laboratory for Molecular Enzymology & Engineering, The Ministry of Education, Jilin University, Changchun, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xu
authors.affiliation: School of Life Sciences, Jilin University, Changchun, PR China; National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun, PR China; Key Laboratory for Molecular Enzymology & Engineering, The Ministry of Education, Jilin University, Changchun, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Kong
authors.affiliation: School of Life Sciences, Jilin University, Changchun, PR China; National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun, PR China; Key Laboratory for Molecular Enzymology & Engineering, The Ministry of Education, Jilin University, Changchun, PR China. Electronic address: jiangcl@jlu.edu.cn.
authors.forename: Chunlai
authors.initials: C
authors.lastname: Jiang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood*; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D045142:Cross-Priming; D004770:Enterovirus / Q000737:chemistry / Q000276:immunology*; D004769:Enterovirus Infections / Q000276:immunology / Q000517:prevention & control*; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D051379:Mice; D009500:Neutralization Tests; D029322:Norovirus / Q000276:immunology*; D022223:Vaccines, Subunit / Q000276:immunology; D058425:Vaccines, Virus-Like Particle / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D036022:Capsid Proteins; D018985:Epitopes, B-Lymphocyte; D022223:Vaccines, Subunit; D058425:Vaccines, Virus-Like Particle; D014765:Viral Vaccines
keywords: Antigen presentation; Enterovirus 71; Epitope; Neutralizing antibody; Norovirus P particle