title: Identification of a conserved linear neutralizing epitope recognized by monoclonal antibody 9A9 against serotype A foot-and-mouth disease virus.
abstract: Foot-and-mouth disease (FMD), caused by foot-and-mouth disease virus (FMDV), is a highly contagious infectious disease that affects domestic and wild cloven-hoofed animals worldwide. In recent years, a series of outbreaks of serotype A FMD have occurred in many countries. High-affinity neutralizing antibodies against a conserved epitope have the potential to provide protective immunity against diverse subtypes of FMDV serotype A and to protect against future pandemics. In this study, we produced an A serotype FMDV-specific monoclonal antibody (MAb) against the viral capsid protein VP1, designated 9A9, that potently neutralized FMDV A/JLYS/CHA/2014 with a 50 % neutralization titer (NT50) of 4,096. GST-fusion proteins expressing truncated peptides of VP1 were subjected to Western blot analysis using MAb 9A9, and it was found that the peptide (143)RGDLGPLAARL(153) of VP1 was the minimal epitope for MAb 9A9 binding. Western blot analysis also revealed that the epitope peptide could be recognized by positive sera from serotype A FMDV-infected pigs and cattle. Subsequent alanine-scanning mutagenesis analysis revealed that residues Gly(147) and Leu(149) of the 9A9-recognized epitope are crucial for MAb 9A9 binding. Furthermore, under immunological pressure selected by MAb 9A9, a single amino acid residue replacement (L149P) occurred in a viral neutralization-escape mutant, which verified the location of a critical residue of this epitope at Leu(149). Importantly, the epitope (143)RGDLGPLAARL(153) was highly conserved among different topotypes of serotype A FMDV strains in sequence alignment analysis. Thus, the results of this study could have application potential in the development of epitope-based vaccines and a suitable MAb-based diagnostic method for detection of type A FMDV as well as quantitation of antibodies against FMDV serotype A.
authors.affiliation: Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, No. 427 Maduan Street, Harbin, 150001, People's Republic of China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Liang
authors.affiliation: Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, No. 427 Maduan Street, Harbin, 150001, People's Republic of China.
authors.forename: Guohui
authors.initials: G
authors.lastname: Zhou
authors.affiliation: Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, No. 427 Maduan Street, Harbin, 150001, People's Republic of China.
authors.forename: Wenming
authors.initials: W
authors.lastname: Liu
authors.affiliation: Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, No. 427 Maduan Street, Harbin, 150001, People's Republic of China.
authors.forename: Baolin
authors.initials: B
authors.lastname: Yang
authors.affiliation: Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, No. 427 Maduan Street, Harbin, 150001, People's Republic of China.
authors.forename: Chaosi
authors.initials: C
authors.lastname: Li
authors.affiliation: Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, No. 427 Maduan Street, Harbin, 150001, People's Republic of China.
authors.forename: Haiwei
authors.initials: H
authors.lastname: Wang
authors.affiliation: Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, No. 427 Maduan Street, Harbin, 150001, People's Republic of China.
authors.forename: Decheng
authors.initials: D
authors.lastname: Yang
authors.affiliation: Institute of Veterinary Medicine, Xinjiang Academy of Animal Science, 151 Eastern Kelamayi Street, Ürümqi, 830000, People's Republic of China.
authors.forename: Wenge
authors.initials: W
authors.lastname: Ma
authors.affiliation: Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, No. 427 Maduan Street, Harbin, 150001, People's Republic of China. liyu@hvri.ac.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Yu
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology*; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology*; D004252:DNA Mutational Analysis; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000235:genetics / Q000276:immunology*; D029544:Foot-and-Mouth Disease Virus / Q000276:immunology*; D057131:Immune Evasion; D008807:Mice, Inbred BALB C; D020125:Mutation, Missense; D009500:Neutralization Tests; D065288:Serogroup
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D036022:Capsid Proteins; D018985:Epitopes, B-Lymphocyte; C442501:VP1 protein, Foot-and-mouth disease virus