title: Protection against lethal enterovirus 71 challenge in mice by a recombinant vaccine candidate containing a broadly cross-neutralizing epitope within the VP2 EF loop.
abstract: Human enterovirus 71 (EV71) is the main causative agent of hand, foot, and mouth disease (HFMD) and is associated with several severe neurological complications in the Asia-Pacific region. Here, we evaluated that while passive transfer of neutralizing monoclonal antibody (nMAb) against the VP2 protein protect against lethal EV71 infection in BALB/c mice. Protective nMAb were mapped to residues 141-155 of VP2 by peptide ELISA. High-resolution structural analysis showed that the epitope is part of the VP2 EF loop, which is the "puff" region that forms the "southern rim" of the canyon. Moreover, a three-dimensional structural characterization for the puff region with prior neutralizing epitopes and receptor-binding sites that can serve to inform vaccine strategies. Interestingly, using hepatitis B virus core protein (HBc) as a carrier, we demonstrated that the cross-neutralizing EV71 antibodies were induced, and the VP2 epitope immunized mice serum also conferred 100% in vivo passive protection. The mechanism of in vivo protection conferred by VP2 nMAb is in part attributed to the in vitro neutralizing titer and ability to bind authentic viral particles. Importantly, the anti-VP2(aa141-155) antibodies could inhibit the binding of human serum to EV71 virions showed that the VP2 epitope is immunodominant. Collectively, our results suggest that a broad-spectrum vaccine strategy targeting the high-affinity epitope of VP2 EF loop may elicits effective immune responses against EV71 infection.
authors.affiliation: 1. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, Xiamen University, Xiamen Fujian, 361102, PR China ; 2. National Institute of Diagnostics and Vaccine Development in infectious diseases, School of Public Health, Xiamen University, Xiamen Fujian, 361102, PR China.
authors.forename: Longfa
authors.initials: L
authors.lastname: Xu
authors.affiliation: 1. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, Xiamen University, Xiamen Fujian, 361102, PR China ; 2. National Institute of Diagnostics and Vaccine Development in infectious diseases, School of Public Health, Xiamen University, Xiamen Fujian, 361102, PR China.
authors.forename: Delei
authors.initials: D
authors.lastname: He
authors.affiliation: 1. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, Xiamen University, Xiamen Fujian, 361102, PR China.
authors.forename: Zhiqun
authors.initials: Z
authors.lastname: Li
authors.affiliation: 1. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, Xiamen University, Xiamen Fujian, 361102, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zheng
authors.affiliation: 1. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, Xiamen University, Xiamen Fujian, 361102, PR China.
authors.forename: Lisheng
authors.initials: L
authors.lastname: Yang
authors.affiliation: 2. National Institute of Diagnostics and Vaccine Development in infectious diseases, School of Public Health, Xiamen University, Xiamen Fujian, 361102, PR China.
authors.forename: Miao
authors.initials: M
authors.lastname: Yu
authors.affiliation: 1. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, Xiamen University, Xiamen Fujian, 361102, PR China ; 2. National Institute of Diagnostics and Vaccine Development in infectious diseases, School of Public Health, Xiamen University, Xiamen Fujian, 361102, PR China.
authors.forename: Hai
authors.initials: H
authors.lastname: Yu
authors.affiliation: 1. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, Xiamen University, Xiamen Fujian, 361102, PR China ; 2. National Institute of Diagnostics and Vaccine Development in infectious diseases, School of Public Health, Xiamen University, Xiamen Fujian, 361102, PR China.
authors.forename: Yixin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: 1. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, Xiamen University, Xiamen Fujian, 361102, PR China ; 2. National Institute of Diagnostics and Vaccine Development in infectious diseases, School of Public Health, Xiamen University, Xiamen Fujian, 361102, PR China.
authors.forename: Yuqiong
authors.initials: Y
authors.lastname: Que
authors.affiliation: 1. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, Xiamen University, Xiamen Fujian, 361102, PR China ; 2. National Institute of Diagnostics and Vaccine Development in infectious diseases, School of Public Health, Xiamen University, Xiamen Fujian, 361102, PR China.
authors.forename: James Wai Kuo
authors.initials: JW
authors.lastname: Shih
authors.affiliation: 2. National Institute of Diagnostics and Vaccine Development in infectious diseases, School of Public Health, Xiamen University, Xiamen Fujian, 361102, PR China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: 1. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, Xiamen University, Xiamen Fujian, 361102, PR China ; 2. National Institute of Diagnostics and Vaccine Development in infectious diseases, School of Public Health, Xiamen University, Xiamen Fujian, 361102, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 1. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, Xiamen University, Xiamen Fujian, 361102, PR China ; 2. National Institute of Diagnostics and Vaccine Development in infectious diseases, School of Public Health, Xiamen University, Xiamen Fujian, 361102, PR China.
authors.forename: Qinjian
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: 1. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, Xiamen University, Xiamen Fujian, 361102, PR China ; 2. National Institute of Diagnostics and Vaccine Development in infectious diseases, School of Public Health, Xiamen University, Xiamen Fujian, 361102, PR China.
authors.forename: Tong
authors.initials: T
authors.lastname: Cheng
authors.affiliation: 1. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, Xiamen University, Xiamen Fujian, 361102, PR China ; 2. National Institute of Diagnostics and Vaccine Development in infectious diseases, School of Public Health, Xiamen University, Xiamen Fujian, 361102, PR China.
authors.forename: Ningshao
authors.initials: N
authors.lastname: Xia
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000097:blood / Q000627:therapeutic use; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D029821:Enterovirus A, Human / Q000235:genetics / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005260:Female; D006232:Hand, Foot and Mouth Disease / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D016019:Survival Analysis; D016896:Treatment Outcome; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D015678:Viral Structural Proteins / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D018985:Epitopes, B-Lymphocyte; D014614:Vaccines, Synthetic; D015678:Viral Structural Proteins; D014765:Viral Vaccines
keywords: Human enterovirus 71; VP2 EF loop; cross-neutralizing linear epitope; epitope peptide vaccine.; therapeutic antibodies