Utilisation of Chimeric Lyssaviruses to Assess Vaccine Protection against Highly Divergent Lyssaviruses

Lyssaviruses constitute a diverse range of viruses with the ability to cause fatal encephalitis known as rabies. Existing human rabies vaccines and post exposure prophylaxes (PEP) are based on inactivated preparations of, and neutralising antibody preparations directed against, classical rabies viru...

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Main Authors: Jennifer S. Evans, Guanghui Wu, David Selden, Hubert Buczkowski, Leigh Thorne, Anthony R. Fooks, Ashley C. Banyard
Format: Article
Language:English
Published: MDPI AG 2018-03-01
Series:Viruses
Subjects:
Online Access:http://www.mdpi.com/1999-4915/10/3/130
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author Jennifer S. Evans
Guanghui Wu
David Selden
Hubert Buczkowski
Leigh Thorne
Anthony R. Fooks
Ashley C. Banyard
author_facet Jennifer S. Evans
Guanghui Wu
David Selden
Hubert Buczkowski
Leigh Thorne
Anthony R. Fooks
Ashley C. Banyard
author_sort Jennifer S. Evans
collection DOAJ
description Lyssaviruses constitute a diverse range of viruses with the ability to cause fatal encephalitis known as rabies. Existing human rabies vaccines and post exposure prophylaxes (PEP) are based on inactivated preparations of, and neutralising antibody preparations directed against, classical rabies viruses, respectively. Whilst these prophylaxes are highly efficient at neutralising and preventing a productive infection with rabies virus, their ability to neutralise other lyssaviruses is thought to be limited. The remaining 15 virus species within the lyssavirus genus have been divided into at least three phylogroups that generally predict vaccine protection. Existing rabies vaccines afford protection against phylogroup I viruses but offer little to no protection against phylogroup II and III viruses. As such, work involving sharps with phylogroup II and III must be considered of high risk as no PEP is thought to have any effect on the prevention of a productive infection with these lyssaviruses. Whilst rabies virus itself has been characterised in a number of different animal models, data on the remaining lyssaviruses are scarce. As the lyssavirus glycoprotein is considered to be the sole target of neutralising antibodies we generated a vaccine strain of rabies using reverse genetics expressing highly divergent glycoproteins of West Caucasian Bat lyssavirus and Ikoma lyssavirus. Using these recombinants, we propose that recombinant vaccine strain derived lyssaviruses containing heterologous glycoproteins may be a suitable surrogate for wildtype viruses when assessing vaccine protection for the lyssaviruses.
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spelling doaj.art-b5bf227bf9c84846a520b6258baa75822022-12-21T18:25:18ZengMDPI AGViruses1999-49152018-03-0110313010.3390/v10030130v10030130Utilisation of Chimeric Lyssaviruses to Assess Vaccine Protection against Highly Divergent LyssavirusesJennifer S. Evans0Guanghui Wu1David Selden2Hubert Buczkowski3Leigh Thorne4Anthony R. Fooks5Ashley C. Banyard6Wildlife Zoonoses and Vector Bourne Disease Research Group, Animal and Plant Health Agency, Woodham Lane, Weybridge, Surrey KT15 3NB, UKWildlife Zoonoses and Vector Bourne Disease Research Group, Animal and Plant Health Agency, Woodham Lane, Weybridge, Surrey KT15 3NB, UKWildlife Zoonoses and Vector Bourne Disease Research Group, Animal and Plant Health Agency, Woodham Lane, Weybridge, Surrey KT15 3NB, UKWildlife Zoonoses and Vector Bourne Disease Research Group, Animal and Plant Health Agency, Woodham Lane, Weybridge, Surrey KT15 3NB, UKWildlife Zoonoses and Vector Bourne Disease Research Group, Animal and Plant Health Agency, Woodham Lane, Weybridge, Surrey KT15 3NB, UKWildlife Zoonoses and Vector Bourne Disease Research Group, Animal and Plant Health Agency, Woodham Lane, Weybridge, Surrey KT15 3NB, UKWildlife Zoonoses and Vector Bourne Disease Research Group, Animal and Plant Health Agency, Woodham Lane, Weybridge, Surrey KT15 3NB, UKLyssaviruses constitute a diverse range of viruses with the ability to cause fatal encephalitis known as rabies. Existing human rabies vaccines and post exposure prophylaxes (PEP) are based on inactivated preparations of, and neutralising antibody preparations directed against, classical rabies viruses, respectively. Whilst these prophylaxes are highly efficient at neutralising and preventing a productive infection with rabies virus, their ability to neutralise other lyssaviruses is thought to be limited. The remaining 15 virus species within the lyssavirus genus have been divided into at least three phylogroups that generally predict vaccine protection. Existing rabies vaccines afford protection against phylogroup I viruses but offer little to no protection against phylogroup II and III viruses. As such, work involving sharps with phylogroup II and III must be considered of high risk as no PEP is thought to have any effect on the prevention of a productive infection with these lyssaviruses. Whilst rabies virus itself has been characterised in a number of different animal models, data on the remaining lyssaviruses are scarce. As the lyssavirus glycoprotein is considered to be the sole target of neutralising antibodies we generated a vaccine strain of rabies using reverse genetics expressing highly divergent glycoproteins of West Caucasian Bat lyssavirus and Ikoma lyssavirus. Using these recombinants, we propose that recombinant vaccine strain derived lyssaviruses containing heterologous glycoproteins may be a suitable surrogate for wildtype viruses when assessing vaccine protection for the lyssaviruses.http://www.mdpi.com/1999-4915/10/3/130lyssavirusrabiesvaccineneutralizing antibodychimeraantigenic
spellingShingle Jennifer S. Evans
Guanghui Wu
David Selden
Hubert Buczkowski
Leigh Thorne
Anthony R. Fooks
Ashley C. Banyard
Utilisation of Chimeric Lyssaviruses to Assess Vaccine Protection against Highly Divergent Lyssaviruses
Viruses
lyssavirus
rabies
vaccine
neutralizing antibody
chimera
antigenic
title Utilisation of Chimeric Lyssaviruses to Assess Vaccine Protection against Highly Divergent Lyssaviruses
title_full Utilisation of Chimeric Lyssaviruses to Assess Vaccine Protection against Highly Divergent Lyssaviruses
title_fullStr Utilisation of Chimeric Lyssaviruses to Assess Vaccine Protection against Highly Divergent Lyssaviruses
title_full_unstemmed Utilisation of Chimeric Lyssaviruses to Assess Vaccine Protection against Highly Divergent Lyssaviruses
title_short Utilisation of Chimeric Lyssaviruses to Assess Vaccine Protection against Highly Divergent Lyssaviruses
title_sort utilisation of chimeric lyssaviruses to assess vaccine protection against highly divergent lyssaviruses
topic lyssavirus
rabies
vaccine
neutralizing antibody
chimera
antigenic
url http://www.mdpi.com/1999-4915/10/3/130
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