Abstract
Foot-and-mouth disease virus (FMDV) causes a highly contagious and devastating disease in livestock animals and has a great potential to cause severe economic loss worldwide. The major antigen of FMDV capsid protein, VP1, contains the major B-cell epitope responsible for effectively eliciting protective humoral immunity. In this study, irradiated Salmonella Typhimurium (KST0666) were used as transgenic vectors containing stress-inducible plasmid pRECN-VP1 to deliver the VP1 protein from FMDV-type A/WH/CHA/09. Mice were orally inoculated with ATOMASal-L3 harboring pRECN-VP1, and FMDV virus-like particles, where (VLPFMDV)-specific humoral, mucosal, and cellular immune responses were evaluated. Mice vaccinated with attenuated Salmonella (KST0666) expressing VP1 (named KST0669) showed high levels of VLP-specific IgA in feces and IgG in serum, with high FMDV neutralization titer. Moreover, KST0669-vaccinated mice showed increased population of IFN-γ (type 1 T helper cells; Th1 cells)-, IL-5 (Th2 cells)-, and IL-17A (Th17 cells)-expressing CD4+ as well as activated CD8+ T cells (IFN-γ+CD8+ cells), detected by stimulating VLPFMDV. All data indicate that our Salmonella vector system successfully delivered FMDV VP1 to immune cells and that the humoral and cellular efficacy of the vaccine can be easily evaluated using VLPFMDV in a Biosafety Level I (BSL1) laboratory.
Highlights
Foot-and-mouth disease (FMD) may result in serious economic losses to the livestock industry by causing abortions, weight loss, and reduced milk production [1,2]
We previously developed an effective bacterial attenuation method using radiation mutation technology (RMT) that can reduce the virulence of pathogenic bacteria without genetic manipulation [38]
KST0666 strain harboring pRECN-VP1 was named as KST0669
Summary
Foot-and-mouth disease (FMD) may result in serious economic losses to the livestock industry by causing abortions, weight loss, and reduced milk production [1,2]. FMD virus (FMDV) is a highly contagious pathogen that causes blisters inside the mouth and bullous lesions on the feet of cloven-hoofed animals [2]. The current FMD vaccines that are commonly used in endemic areas contain inactivated whole-virus with binary ethyleneimine (BEI) or formaldehyde, followed by formulating with an oil-based adjuvant [7,8]. The currently available vaccines have been shown to reduce FMDV prevalence in endemic areas, they have several limitations: (1) the requirement of a Biosafety Level III (BSL3) facilities for mass production of the virus antigen, (2) extensive genetic variation during manufacturing process, (3) short-term immunity due to lower immunogenicity, (4) lower cross-protective immunity against heterogenous serotypes and subtypes [9,10]. Other important concerns regarding inactivated vaccines include multiple vaccination, cold chains, and accidental viral release from manufacturing facility [11]
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