Characterisation of a Live-Attenuated Rabies Virus Expressing a Secreted scFv for the Treatment of Rabies
Rabies virus (RABV) causes possibly the oldest disease and is responsible for an estimated >59,000 human fatalities/year. Post exposure prophylaxis (PEP), the administration of vaccine and rabies immunoglobulin, is a highly effective tool which is frequently unavailable in RABV endemic areas. Fur...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-07-01
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| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/15/8/1674 |
| _version_ | 1827728484862001152 |
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| author | Samuel P. Smith Rebecca Shipley Pascal Drake Anthony R. Fooks Julian Ma Ashley C. Banyard |
| author_facet | Samuel P. Smith Rebecca Shipley Pascal Drake Anthony R. Fooks Julian Ma Ashley C. Banyard |
| author_sort | Samuel P. Smith |
| collection | DOAJ |
| description | Rabies virus (RABV) causes possibly the oldest disease and is responsible for an estimated >59,000 human fatalities/year. Post exposure prophylaxis (PEP), the administration of vaccine and rabies immunoglobulin, is a highly effective tool which is frequently unavailable in RABV endemic areas. Furthermore, due to the constraints of the blood-brain barrier, current PEP regimes are ineffective after the onset of clinical symptoms which invariably result in death. To circumvent this barrier, a live-attenuated recombinant RABV expressing a highly RABV-neutralising scFv antibody (62-71-3) linked to the fluorescent marker mCherry was designed. Once rescued, the resulting construct (named RABV-62scFv) was grown to high titres, its growth and cellular dissemination kinetics characterised, and the functionality of the recombinant 62-71-3 scFv assessed. Encouraging scFv production and subsequent virus neutralisation results demonstrate the potential for development of a therapeutic live-attenuated virus-based post-infection treatment (PIT) for RABV infection. |
| first_indexed | 2024-03-10T23:30:47Z |
| format | Article |
| id | doaj.art-8404f8f9cba942df8aa4a1918725e90c |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T23:30:47Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-8404f8f9cba942df8aa4a1918725e90c2023-11-19T03:20:06ZengMDPI AGViruses1999-49152023-07-01158167410.3390/v15081674Characterisation of a Live-Attenuated Rabies Virus Expressing a Secreted scFv for the Treatment of RabiesSamuel P. Smith0Rebecca Shipley1Pascal Drake2Anthony R. Fooks3Julian Ma4Ashley C. Banyard5Wildlife Zoonoses and Vector-Borne Diseases Research Group, Animal and Plant Health Agency (APHA), Weybridge, London KT15 3NB, UKWildlife Zoonoses and Vector-Borne Diseases Research Group, Animal and Plant Health Agency (APHA), Weybridge, London KT15 3NB, UKInstitute for Infection and Immunity, St. George’s Hospital Medical School, University of London, London SW17 0RE, UKWildlife Zoonoses and Vector-Borne Diseases Research Group, Animal and Plant Health Agency (APHA), Weybridge, London KT15 3NB, UKInstitute for Infection and Immunity, St. George’s Hospital Medical School, University of London, London SW17 0RE, UKWildlife Zoonoses and Vector-Borne Diseases Research Group, Animal and Plant Health Agency (APHA), Weybridge, London KT15 3NB, UKRabies virus (RABV) causes possibly the oldest disease and is responsible for an estimated >59,000 human fatalities/year. Post exposure prophylaxis (PEP), the administration of vaccine and rabies immunoglobulin, is a highly effective tool which is frequently unavailable in RABV endemic areas. Furthermore, due to the constraints of the blood-brain barrier, current PEP regimes are ineffective after the onset of clinical symptoms which invariably result in death. To circumvent this barrier, a live-attenuated recombinant RABV expressing a highly RABV-neutralising scFv antibody (62-71-3) linked to the fluorescent marker mCherry was designed. Once rescued, the resulting construct (named RABV-62scFv) was grown to high titres, its growth and cellular dissemination kinetics characterised, and the functionality of the recombinant 62-71-3 scFv assessed. Encouraging scFv production and subsequent virus neutralisation results demonstrate the potential for development of a therapeutic live-attenuated virus-based post-infection treatment (PIT) for RABV infection.https://www.mdpi.com/1999-4915/15/8/1674rabieslyssavirusvirus attenuationPEPantibodyscFv |
| spellingShingle | Samuel P. Smith Rebecca Shipley Pascal Drake Anthony R. Fooks Julian Ma Ashley C. Banyard Characterisation of a Live-Attenuated Rabies Virus Expressing a Secreted scFv for the Treatment of Rabies Viruses rabies lyssavirus virus attenuation PEP antibody scFv |
| title | Characterisation of a Live-Attenuated Rabies Virus Expressing a Secreted scFv for the Treatment of Rabies |
| title_full | Characterisation of a Live-Attenuated Rabies Virus Expressing a Secreted scFv for the Treatment of Rabies |
| title_fullStr | Characterisation of a Live-Attenuated Rabies Virus Expressing a Secreted scFv for the Treatment of Rabies |
| title_full_unstemmed | Characterisation of a Live-Attenuated Rabies Virus Expressing a Secreted scFv for the Treatment of Rabies |
| title_short | Characterisation of a Live-Attenuated Rabies Virus Expressing a Secreted scFv for the Treatment of Rabies |
| title_sort | characterisation of a live attenuated rabies virus expressing a secreted scfv for the treatment of rabies |
| topic | rabies lyssavirus virus attenuation PEP antibody scFv |
| url | https://www.mdpi.com/1999-4915/15/8/1674 |
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