Adeyemi, OO orcid.org/0000-0002-0848-5917, Nicol, C, Stonehouse, NJ orcid.org/0000-0003-1146-5519 et al. (1 more author) (2017) Increasing type-1 poliovirus capsid stability by thermal selection. Journal of Virology, 91 (4). e01586-16. ISSN 0022-538X
Abstract
Poliomyelitis is a highly infectious disease caused by poliovirus (PV). It can result in paralysis and may be fatal. Integrated global immunisation programmes using live-attenuated oral (OPV) and/or inactivated PV vaccines (IPV) have systematically reduced its spread and paved the way for eradication. Immunisation will continue post-eradication to ensure against reintroduction of the disease, but there are biosafety concerns for both OPV and IPV. These could be addressed by the production and use of virus-free virus-like particle (VLP) vaccines which mimic the ‘empty' capsids (ECs) normally produced in viral infection. Although ECs are antigenically indistinguishable from mature virus particles, they are less stable and readily convert to an alternative conformation unsuitable for vaccine purposes. Stabilised ECs, expressed recombinantly as VLPs, could be ideal candidate vaccines for a polio-free world. However, although genome-free PV ECs have been expressed as VLPs in a variety of systems, their inherent antigenic instability has proved a barrier to further development. In this study, we have selected thermally-stable ECs of type-1 PV (PV-1). The ECs are antigenically stable at temperatures above the conversion temperature of wild type (wt) virion. We have identified mutations on the capsid surface and internal networks that are responsible for the EC stability. With reference to the capsid structure, we speculate on the roles of these residues in capsid stability and postulate that such stabilised VLPs could be used as novel vaccines. Importance: Poliomyelitis is a highly infectious disease caused by PV and is on the verge of eradication. There are biosafety concerns of reintroduction of the disease from current vaccines which require live virus for production. Recombinantly-expressed virus-like particles could address these inherent problems. However, the genome-free capsids (ECs) of wt PV are unstable and readily change antigenicity to a form not suitable as a vaccine. Here, we demonstrate that the ECs of type-1 PV can be stabilised by selecting heat-resistant viruses. Our data show that some capsid mutations stabilise the ECs and could be applied as candidates to synthesise stable virus-like particles (VLPs) as future genome-free poliovirus vaccines.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016 Adeyemi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. |
Keywords: | VLP; heat stable; poliovirus |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Molecular Virology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 22 Dec 2016 10:38 |
Last Modified: | 05 Oct 2017 16:50 |
Published Version: | https://doi.org/10.1128/JVI.01586-16 |
Status: | Published |
Publisher: | American Society for Microbiology |
Identification Number: | 10.1128/JVI.01586-16 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:109815 |