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Large-scale production of foot-and-mouth disease virus (serotype Asia1) VLP vaccine in Escherichia coli and protection potency evaluation in cattle

Xiao, Yan, Chen, Hong-Ying, Wang, Yuzhou, Yin, Bo, Lv, Chaochao, Mo, Xiaobing, Yan, He, Xuan, Yajie, Huang, Yuxin, Pang, Wenqiang, Li, Xiangdong, Yuan, Y. Adam, Tian, Kegong
BMC biotechnology 2016 v.16 no.1 pp. 56
Escherichia coli, Foot-and-mouth disease virus, adjuvants, cattle, chromatography, coat proteins, enzyme-linked immunosorbent assay, fermentation, foot-and-mouth disease, neutralizing antibodies, plasmids, protein synthesis, serotypes, subunit vaccines, vaccination, virus-like particle vaccines, virus-like particles
BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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.