title: Large-scale production of foot-and-mouth disease virus (serotype Asia1) VLP vaccine in Escherichia coli and protection potency evaluation in cattle.
abstract: Foot-and-mouth disease (FMD) is an acute, highly contagious disease that infects cloven-hoofed animals. Vaccination is an effective means of preventing and controlling FMD. Compared to conventional inactivated FMDV vaccines, the format of FMDV virus-like particles (VLPs) as a non-replicating particulate vaccine candidate is a promising alternative.
  
  
  
  In this study, we have developed a co-expression system in E. coli, which drove the expression of FMDV capsid proteins (VP0, VP1, and VP3) in tandem by a single plasmid. The co-expressed FMDV capsid proteins (VP0, VP1, and VP3) were produced in large scale by fermentation at 10 L scale and the chromatographic purified capsid proteins were auto-assembled as VLPs in vitro. Cattle vaccinated with a single dose of the subunit vaccine, comprising in vitro assembled FMDV VLP and adjuvant, developed FMDV-specific antibody response (ELISA antibodies and neutralizing antibodies) with the persistent period of 6 months. Moreover, cattle vaccinated with the subunit vaccine showed the high protection potency with the 50 % bovine protective dose (PD50) reaching 11.75 PD50 per dose.
  
  
  
  Our data strongly suggest that in vitro assembled recombinant FMDV VLPs produced from E. coli could function as a potent FMDV vaccine candidate against FMDV Asia1 infection. Furthermore, the robust protein expression and purification approaches described here could lead to the development of industrial level large-scale production of E. coli-based VLPs against FMDV infections with different serotypes.
authors.affiliation: National Research Center for Veterinary Medicine, Road Cuiwei, High-Tech District, Luoyang, 471003, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: National University of Singapore (Suzhou) Research Institute, 377 Lin Quan Street, Suzhou Industrial Park, Jiangsu, 215123, China.
authors.forename: Hong-Ying
authors.initials: HY
authors.lastname: Chen
authors.affiliation: National Research Center for Veterinary Medicine, Road Cuiwei, High-Tech District, Luoyang, 471003, People's Republic of China.
authors.forename: Yuzhou
authors.initials: Y
authors.lastname: Wang
authors.affiliation: National University of Singapore (Suzhou) Research Institute, 377 Lin Quan Street, Suzhou Industrial Park, Jiangsu, 215123, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yin
authors.affiliation: National Research Center for Veterinary Medicine, Road Cuiwei, High-Tech District, Luoyang, 471003, People's Republic of China.
authors.forename: Chaochao
authors.initials: C
authors.lastname: Lv
authors.affiliation: National University of Singapore (Suzhou) Research Institute, 377 Lin Quan Street, Suzhou Industrial Park, Jiangsu, 215123, China.|Department of Biological Sciences and Centre for Bioimaging Sciences, National University of Singapore, 14 Science Drive 4, Singapore, 117543, Singapore.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Mo
authors.affiliation: National Research Center for Veterinary Medicine, Road Cuiwei, High-Tech District, Luoyang, 471003, People's Republic of China.
authors.forename: He
authors.initials: H
authors.lastname: Yan
authors.affiliation: National Research Center for Veterinary Medicine, Road Cuiwei, High-Tech District, Luoyang, 471003, People's Republic of China.
authors.forename: Yajie
authors.initials: Y
authors.lastname: Xuan
authors.affiliation: National Research Center for Veterinary Medicine, Road Cuiwei, High-Tech District, Luoyang, 471003, People's Republic of China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Huang
authors.affiliation: National Research Center for Veterinary Medicine, Road Cuiwei, High-Tech District, Luoyang, 471003, People's Republic of China.
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Pang
authors.affiliation: National Research Center for Veterinary Medicine, Road Cuiwei, High-Tech District, Luoyang, 471003, People's Republic of China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Li
authors.affiliation: National University of Singapore (Suzhou) Research Institute, 377 Lin Quan Street, Suzhou Industrial Park, Jiangsu, 215123, China. dbsyya@nusri.cn.|Department of Biological Sciences and Centre for Bioimaging Sciences, National University of Singapore, 14 Science Drive 4, Singapore, 117543, Singapore. dbsyya@nusri.cn.
authors.forename: Y Adam
authors.initials: YA
authors.lastname: Yuan
authors.affiliation: National Research Center for Veterinary Medicine, Road Cuiwei, High-Tech District, Luoyang, 471003, People's Republic of China. tiankg@263.net.|College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan, 450002, People's Republic of China. tiankg@263.net.
authors.forename: Kegong
authors.initials: K
authors.lastname: Tian
mesh_terms: D000818:Animals; D061249:Batch Cell Culture Techniques / Q000379:methods; D002417:Cattle; D002418:Cattle Diseases / Q000517:prevention & control* / Q000821:virology*; D004926:Escherichia coli / Q000235:genetics; D005536:Foot-and-Mouth Disease / Q000517:prevention & control* / Q000821:virology*; D015202:Protein Engineering / Q000379:methods; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D058425:Vaccines, Virus-Like Particle / Q000096:biosynthesis* / Q000235:genetics / Q000627:therapeutic use
chemical_list: D011994:Recombinant Proteins; D058425:Vaccines, Virus-Like Particle
keywords: Fifty percent protection dose (PD50); Foot-and-mouth disease; Large scale production in E. coli; Serotype Asia 1; Virus-like particle vaccine