Generation of Antibodies against Foot-and-Mouth-Disease Virus Capsid Protein VP4 Using Hepatitis B Core VLPs as a Scaffold.

Jessica Swanson,Joseph Newman,Philippa C Hawes,Rennos Fragkoudis,Alison Burman,Tobias J Tuthill,Anusha Panjwani,Nicola J Stonehouse

doi:10.3390/life11040338

Jessica Swanson, Joseph Newman + Show 6 more

Open Access

https://doi.org/10.3390/life11040338

Copy DOI

Abstract

The picornavirus foot-and-mouth disease virus (FMDV) is the causative agent of the economically important disease of livestock, foot-and-mouth disease (FMD). VP4 is a highly conserved capsid protein, which is important during virus entry. Previous published work has shown that antibodies targeting the N-terminus of VP4 of the picornavirus human rhinovirus are broadly neutralising. In addition, previous studies showed that immunisation with the N-terminal 20 amino acids of enterovirus A71 VP4 displayed on the hepatitis B core (HBc) virus-like particles (VLP) can induce cross-genotype neutralisation. To investigate if a similar neutralising response against FMDV VP4 could be generated, HBc VLPs displaying the N-terminus of FMDV VP4 were designed. The N-terminal 15 amino acids of FMDV VP4 was inserted into the major immunodominant region. HBc VLPs were also decorated with peptides of the N-terminus of FMDV VP4 attached using a HBc-spike binding tag. Both types of VLPs were used to immunise mice and the resulting serum was investigated for VP4-specific antibodies. The VLP with VP4 inserted into the spike, induced VP4-specific antibodies, however the VLPs with peptides attached to the spikes did not. The VP4-specific antibodies could recognise native FMDV, but virus neutralisation was not demonstrated. This work shows that the HBc VLP presents a useful tool for the presentation of FMDV capsid epitopes.

Highlights

Foot-and-mouth disease virus (FMDV) is the causative agent of foot-and-mouth disease, an economically important disease of livestock such as cattle and pigs [1]
VP4 inserted within the major immunodominant region (MIR) and hepatitis B core (HBc) virus-like particles (VLP) without insertion at the MIR, were expressed in E. coli and purified by sedimentation through sucrose density gradients
VLPs provide an interesting alternative to whole virus particles for dissecting capsid antigenicity and function and could even be useful tools in controlling economically important diseases such as FMDV

Summary

Introduction

Foot-and-mouth disease virus (FMDV) is the causative agent of foot-and-mouth disease, an economically important disease of livestock such as cattle and pigs [1]. FMDV is endemic in large regions of the African and Asian continents, contributing to poverty and poor nutrition in rural communities and limiting trade opportunities for these countries [3]. There are seven distinct serotypes of FMDV Serotype A is considered the most diverse and contains three geographically distinct topotypes and across these there are 26 distinct genotypes [4,5]. This creates a problem for vaccination programs, as there is little cross-protection from the vaccine between different genotypes of the same serotype

Methods

Results

Conclusion