Phoolcharoen, W; Banyard, AC; Prehaud, C; Selden, D; Wu, G; Birch, CPD; Szeto, TH; Lafon, M; Fooks, AR; Ma, JK-C
(2019)
In vitro and in vivo evaluation of a single chain antibody fragment generated in planta with potent rabies neutralisation activity.
Vaccine, 37 (33).
pp. 4673-4680.
ISSN 1873-2518
https://doi.org/10.1016/j.vaccine.2018.02.057
SGUL Authors: Ma, Julian
Abstract
Rabies causes more than 60,000 human deaths annually in areas where the virus is endemic. Importantly, rabies is one of the few pathogens for which there is no treatment following the onset of clinical disease with the outcome of infection being death in almost 100% of cases. Whilst vaccination, and the combination of vaccine and rabies immunoglobulin treatment for post-exposure administration are available, no tools have been identified that can reduce or prevent rabies virus replication once clinical disease has initiated. The search for effective antiviral molecules to treat those that have already developed clinical disease associated with rabies virus infection is considered one of the most important goals in rabies research. The current study assesses a single chain antibody molecule (ScFv) based on a monoclonal antibody that potently neutralises rabies in vitro as a potential therapeutic candidate. The recombinant ScFv was generated in Nicotiana benthamiana by transient expression, and was chemically conjugated (ScFv/RVG) to a 29 amino acid peptide, specific for nicotinic acetylcholine receptor (nAchR) binding in the CNS. This conjugated molecule was able to bind nAchR in vitro and enter neuronal cells more efficiently than ScFv. The ability of the ScFv/RVG to neutralise virus in vivo was assessed using a staggered administration where the molecule was inoculated either four hours before, two days after or four days after infection. The ScFv/RVG conjugate was evaluated in direct comparison with HRIG and a potential antiviral molecule, Favipiravir (also known as T-705) to indicate whether there was greater bioavailability of the ScFv in the brains of treated mice. The study indicated that the approach taken with the ScFv/RVG conjugate may have utility in the design and implementation of novel tools targetting rabies virus infection in the brain.
Item Type: |
Article
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Additional Information: |
© 2018 The Authors. Published by Elsevier Ltd.
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
Keywords: |
Blood brain barrier (BBB), Clinical disease, Immunoglobulin, N-acetylcholine receptor, Nicotiana benthamiana, Rabies virus, Single-chain antibody (ScFv), Virology, 06 Biological Sciences, 07 Agricultural And Veterinary Sciences, 11 Medical And Health Sciences |
SGUL Research Institute / Research Centre: |
Academic Structure > Infection and Immunity Research Institute (INII) |
Journal or Publication Title: |
Vaccine |
ISSN: |
1873-2518 |
Language: |
eng |
Dates: |
Date | Event |
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6 March 2018 | Published Online | 2 August 2019 | Published | 15 February 2018 | Accepted |
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Publisher License: |
Creative Commons: Attribution 4.0 |
Projects: |
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PubMed ID: |
29523449 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/109641 |
Publisher's version: |
https://doi.org/10.1016/j.vaccine.2018.02.057 |
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