Foot-and-mouth disease virus-like particles produced by a SUMO fusion protein system in Escherichia coli induce potent protective immune responses in guinea pigs, swine and cattle

Hui-Chen Guo,Hong Yin,Jian-Xun Luo,Jun-Wu Ma,Xiang-Tao Liu,Ding Xiang Liu,Shun-Li Yang,Ye Jin,De-Hui Sun,Zai-Xin Liu,Shi-Qi Sun,Yan-Quan Wei,Jian-Hong Guo,Shuang-Hui Yin

doi:10.1186/1297-9716-44-48

Abstract

Foot-and-mouth disease virus (FMDV) causes a highly contagious infection in cloven-hoofed animals. The format of FMD virus-like particles (VLP) as a non-replicating particulate vaccine candidate is a promising alternative to conventional inactivated FMDV vaccines. In this study, we explored a prokaryotic system to express and assemble the FMD VLP and validated the potential of VLP as an FMDV vaccine candidate. VLP composed entirely of FMDV (Asia1/Jiangsu/China/2005) capsid proteins (VP0, VP1 and VP3) were simultaneously produced as SUMO fusion proteins by an improved SUMO fusion protein system in E. coli. Proteolytic removal of the SUMO moiety from the fusion proteins resulted in the assembly of VLP with size and shape resembling the authentic FMDV. Immunization of guinea pigs, swine and cattle with FMD VLP by intramuscular inoculation stimulated the FMDV-specific antibody response, neutralizing antibody response, T-cell proliferation response and secretion of cytokine IFN-γ. In addition, immunization with one dose of the VLP resulted in complete protection of these animals from homologous FMDV challenge. The 50% protection dose (PD50) of FMD VLP in cattle is up to 6.34. These results suggest that FMD VLP expressed in E. coli are an effective vaccine in guinea pigs, swine and cattle and support further development of these VLP as a vaccine candidate for protection against FMDV.

Highlights

Foot-and-mouth disease (FMD) is an acute, highly contagious viral disease, which may cause severe economic losses in susceptible cloven-hoofed animals [1,2]
The results show that FMDVspecific antibodies, neutralizing antibodies, specific T-cell response and IFN-γ responses were efficiently induced by immunization with FMD virus-like particles (VLP)
In this study, we attempt to produce the FMD VLP in E. coli and use this VLP preparation as a vaccine candidate for the first time to characterize the immunological properties in a laboratory animal model and in two natural Foot-and-mouth disease virus (FMDV) host animal species, swine and cattle

Summary

Introduction

Foot-and-mouth disease (FMD) is an acute, highly contagious viral disease, which may cause severe economic losses in susceptible cloven-hoofed animals [1,2]. VLP are virus-sized particles with the supra-molecular structures that have the form of rods or icosahedrons [9] They are composed of multiple copies of one or more recombinant expressed viral structural proteins which spontaneously assemble into particles without incorporation of the viral genome. They display antigens in an ordered and repetitive way, inducing rapid, robust humoral immune responses as well as efficient T-cell responses [10]. Several gene-fusion systems, such as NusA, maltose binding protein (MBP), glutathione-S -transferase (GST), ubiquitin (UB), and thioredoxin (Trx), have been developed [25,26]. Small ubiquitinlike modifier (SUMO) protein, a ubiquitin-related protein, has emerged as an effective biotechnological tool, since SUMO usually promotes correct folding and structural stability of the fusion proteins, leading to enhanced functional production of the partner proteins compared to its untagged version [30]

Methods

Results

Conclusion