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

• Published in: BMC biotechnology Vol. 16; no. 1; p. 56
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 02-07-2016; BioMed Central
• Subjects: Animals; Antibiotics; Batch Cell Culture Techniques - methods; Care and treatment; Cattle; Cattle Diseases - prevention & control; Cattle Diseases - virology; Chromatography; Cloning; E coli; Escherichia coli; Escherichia coli - genetics; Fermentation; Foot & mouth disease; Foot-and-mouth disease; Foot-and-Mouth Disease - prevention & control; Foot-and-Mouth Disease - virology; Health aspects; Plasmids; Protein Engineering - methods; Proteins; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Vaccines; Vaccines, Virus-Like Particle - biosynthesis; Vaccines, Virus-Like Particle - genetics; Vaccines, Virus-Like Particle - therapeutic use; United States > US; Asia; Serotype Asia 1; Foot-and-mouth disease; Virus-like particle vaccine; Fifty percent protection dose (PD50); Large scale production in E. coli
• ISSN: 1472-6750; 1472-6750
• DOI: 10.1186/s12896-016-0285-6

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.