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

Jennifer Evans,Ashley Banyard,Hubert Buczkowski,Anthony Fooks,Guanghui Wu,David Selden,Leigh Thorne

doi:10.3390/v10030130

Jennifer Evans, Ashley Banyard + Show 5 more

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https://doi.org/10.3390/v10030130

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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.

Highlights

The lyssavirus genus is a group of high consequence pathogens with, following the onset of clinical disease, a near 100% fatality rate
The SN strain is based on the street Alabama Dufferin (SAD) B19 vaccine strain of rabies as described previously [20,21,22,23,24]
The peak titres of the recombinant viruses reached titres comparable to previously generated recombinants that used the same vaccine backbone with the heterologous G from the European bat lyssaviruses (EBLVs) [21]

Summary

Introduction

The lyssavirus genus is a group of high consequence pathogens with, following the onset of clinical disease, a near 100% fatality rate. Rabies virus (RABV), the prototype lyssavirus, causes over 59,000 human deaths annually, with the majority of the fatalities being in Africa and Asia [1]. This figure is believed to be a gross underestimate as a large proportion of rabies deaths occur in resource limited areas that lack medical facilities and adequate reporting systems to record human cases of rabies [2,3]. The main mode of transmission is through mechanical transfer, most often following the bite of an infected dog Interestingly these pathogens have been isolated across the globe from a variety of mammalian species with 14 of the 16 proposed lyssavirus species being detected in bats [6].

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