Application of Heparin Affinity Chromatography to Produce a Differential Vaccine without Eliciting Antibodies against the Nonstructural Proteins of the Serotype O Foot-and-Mouth Disease Viruses.

Hyejin Kim,Jung-Won Park,Jong-Hyeon Park,Ah-Young Kim,Young-Joon Ko,Sang Hyun Park,Choi-Kyu Park,Jung-Min Lee,Sun Young Park,Jae-Seok Kim

doi:10.3390/v12121405

Hyejin Kim, Jung-Won Park + Show 8 more

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https://doi.org/10.3390/v12121405

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Abstract

Although polyethylene glycol (PEG) application is the most widely used method in removing nonstructural proteins (NSPs) for foot-and-mouth disease (FMD) vaccine production, some NSPs remaining in the antigen could elicit antibodies against these proteins after repeated vaccinations in livestock. Therefore, the purpose of this study was to purify the FMD virus (FMDV) via affinity chromatography using a heparin ligand to remove most proteins, including NSPs. Chromatography showed an intact virus (146S) particle recovery of 70% or more for three different strains of serotype O FMDV (two locally isolated strains and one genetically modified strain). The experimental vaccine made with antigens eluted via heparin affinity chromatography elicited virus-neutralizing antibodies against homologous viruses but did not induce antibodies against NSPs even after five immunizations in goats; this indicated that the NSPs were effectively removed from the vaccine antigen. This method can then be used to produce a higher-quality vaccine compared with PEG application in terms of the purity of the FMD vaccine. Therefore, this result would be an important groundwork for advanced FMD vaccine manufacturing in the near future.

Highlights

Foot-and-mouth disease (FMD) is a highly contagious vesicular disease affecting cloven-hoofed animals and often causes enormous economic loss in the livestock industry [1].The foot-and-mouth disease (FMD) virus (FMDV), the causative agent of FMD, belongs to the Aphthovirus genus of the Picornaviridae family [2]
The purpose of this study was to purify FMD virus (FMDV) by heparin affinity chromatography without nonessential proteins, including nonstructural proteins (NSPs), and the purity of the FMD vaccine prepared with purified FMDV was verified by evaluating NSP antibodies after repeated immunization in goats
The other strain was a genetically engineered virus called the FMDV Om-O-PanAsia2 recombinant strain that was made from a recombination of the backbone region of the O1 Manisa/Turkey/69 strain with the P1 region only being replaced by the O PAK/44/2008 strain [16]

Summary

Introduction

Foot-and-mouth disease (FMD) is a highly contagious vesicular disease affecting cloven-hoofed animals and often causes enormous economic loss in the livestock industry [1]. The FMD virus (FMDV), the causative agent of FMD, belongs to the Aphthovirus genus of the Picornaviridae family [2]. It has a positive-sense, single-stranded RNA genome that is translated into a polyprotein, which is further cleaved into structural proteins (SPs) and nonstructural proteins (NSPs) [3,4,5]. It has imported FMD vaccines annually from Argentina, the UK, and Russia and has set out to develop a domestic FMD vaccine using local virus isolates [7]

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