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

1
Wildlife Zoonoses and Vector Bourne Disease Research Group, Animal and Plant Health Agency, Woodham Lane, Weybridge, Surrey KT15 3NB, UK
2
University of Warwick, Gibbet Hill Road, Coventry, West Midlands CV4 7AL, UK
3
Institute for Infection and Immunity, St. George’s Hospital Medical School, University of London, London SW17 0RE, UK
*
Author to whom correspondence should be addressed.
Viruses 2018, 10(3), 130; https://doi.org/10.3390/v10030130
Received: 2 March 2018 / Revised: 13 March 2018 / Accepted: 13 March 2018 / Published: 15 March 2018
(This article belongs to the Section Animal Viruses)
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Abstract

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. View Full-Text
Keywords: lyssavirus; rabies; vaccine; neutralizing antibody; chimera; antigenic lyssavirus; rabies; vaccine; neutralizing antibody; chimera; antigenic
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Evans, J.S.; Wu, G.; Selden, D.; Buczkowski, H.; Thorne, L.; Fooks, A.R.; Banyard, A.C. Utilisation of Chimeric Lyssaviruses to Assess Vaccine Protection against Highly Divergent Lyssaviruses. Viruses 2018, 10, 130.

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