Abstract

BackgroundFoot-and-mouth disease (FMD) is a highly contagious disease of livestock which causes severe economic loss in cloven-hoofed animals. Vaccination is still a major strategy in developing countries to control FMD. Currently, inactivated vaccine of FMDV has been used in many countries with limited success and safety concerns. Development of a novel effective vaccine is must.MethodsIn the present study, two recombinant pseudotype baculoviruses, one expressing the capsid of foot-and-mouth disease virus (FMDV) under the control of a cytomegalovirus immediate early enhancer/promoter (CMV-IE), and the other the caspid plus a T-cell immunogen coding region under a CAG promoter were constructed, and their expression was characterized in mammalian cells. In addition, their immunogenicity in a mouse model was investigated. The humoral and cell-mediated immune responses induced by pseudotype baculovirus were compared with those of inactivated vaccine.ResultsIndirect immunofluorescence assay (IFA) and indirect sandwich-ELISA (IS-ELISA) showed both recombinant baculoviruses (with or without T-cell epitopes) were transduced efficiently and expressed target proteins in BHK-21 cells. In mice, intramuscular inoculation of recombinants with 1 × 109 or 1 × 1010 PFU/mouse induced the production of FMDV-specific neutralizing antibodies and gamma interferon (IFN-γ). Furthermore, recombinant baculovirus with T-cell epitopes had better immunogenicity than the recombinant without T-cell epitopes as demonstrated by significantly enhanced IFN-γ production (P < 0.01) and higher neutralizing antibody titer (P < 0.05). Although the inactivated vaccine produced the highest titer of neutralizing antibodies, a lower IFN-γ expression was observed compared to the two recombinant pseudotype baculoviruses.ConclusionsThese results indicate that pseudotype baculovirus-mediated gene delivery could be a alternative strategy to develop a new generation of vaccines against FMDV infection.

Highlights

  • Foot-and-mouth disease (FMD) is a highly contagious disease of livestock which causes severe economic loss in cloven-hoofed animals

  • The causative agent is foot-and-mouth disease virus (FMDV) which belongs to the genus Aphthovirus in the family Picornaviridae [1]

  • Since Hofmann reported that recombinant baculovirus containing the cytomegalovirus immediate-early promoter (CMV-IE) was able to drive the expression of a reporter gene in human hepatocytes, baculovirus with a strong mammalian promoter has been used as a novel vector to transfer and express foreign genes in mammalian cells for vaccine development [5,6,7]

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Summary

Introduction

Foot-and-mouth disease (FMD) is a highly contagious disease of livestock which causes severe economic loss in cloven-hoofed animals. Since Hofmann reported that recombinant baculovirus containing the cytomegalovirus immediate-early promoter (CMV-IE) was able to drive the expression of a reporter gene in human hepatocytes, baculovirus with a strong mammalian promoter has been used as a novel vector to transfer and express foreign genes in mammalian cells for vaccine development [5,6,7]. This vector was shown to be capable of carrying large inserts and infecting a variety of cell lines without any apparent viral replication or cytopathic effects, even at a high multiplicity of infection (MOI) [7,8]. It has been reported that a pseudotype baculovirus displaying the glycoprotein of vesicular stomatitis virus (VSV-G) on the envelope can extend the host range, increase the transduction efficiency, and prolong the baculovirusmediated expression in mammalian cells [9,10]

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