Assessing Rabies Vaccine Protection against a Novel Lyssavirus, Kotalahti Bat Lyssavirus.

Rebecca Shipley,Daniel L Horton,Ashley C Banyard,Edward Wright,Fabian Z X Lean,Anthony R Fooks,David Selden

doi:10.3390/v13050947

Abstract

Rabies is a fatal encephalitis caused by an important group of viruses within the Lyssavirus genus. The prototype virus, rabies virus, is still the most commonly reported lyssavirus and causes approximately 59,000 human fatalities annually. The human and animal burden of the other lyssavirus species is undefined. The original reports for the novel lyssavirus, Kotalahti bat lyssavirus (KBLV), were based on the detection of viral RNA alone. In this report we describe the successful generation of a live recombinant virus, cSN-KBLV; where the full-length genome clone of RABV vaccine strain, SAD-B19, was constructed with the glycoprotein of KBLV. Subsequent in vitro characterisation of cSN-KBLV is described here. In addition, the ability of a human rabies vaccine to confer protective immunity in vivo following challenge with this recombinant virus was assessed. Naïve or vaccinated mice were infected intracerebrally with a dose of 100 focus-forming units/30 µL of cSN-KBLV; all naïve mice and 8% (n = 1/12) of the vaccinated mice succumbed to the challenge, whilst 92% (n = 11/12) of the vaccinated mice survived to the end of the experiment. This report provides strong evidence for cross-neutralisation and cross-protection of cSN-KBLV using purified Vero cell rabies vaccine.

Highlights

Rabies is caused by viruses classified within the Lyssavirus genus, family Rhabdoviridae, order Mononegavirales [1]
The present study describes the development of a live recombinant rabies virus (RABV) where the RABV G has been replaced by Kotalahti bat lyssavirus (KBLV) G
Harvested virus was titrated in which the cSNKBLV grew to a peak titre of 2.5 × 104 focus forming units per mL (ffu/mL) whilst the parent cSN strain grew to a peak titre of 1.6 × 106 ffu/mL

Summary

Introduction

Rabies is caused by viruses classified within the Lyssavirus genus, family Rhabdoviridae, order Mononegavirales [1] These viruses are of importance to both human and animal health given the invariably fatal outcome from developing a neurological disease [2]. Within the Lyssavirus genus, the most broadly distributed and important to veterinary and public health is the rabies virus (RABV) Though this virus has largely been eliminated throughout western Europe, RABV is still the most commonly reported lyssavirus. The human and animal burden of the other lyssaviruses, is largely undefined, with only 14 human lyssavirus-related deaths being reported [13,14] This low number of reported cases may be because diagnostic capabilities often reliant on antigen detection or a clinical diagnosis, in endemic areas, are unable to distinguish between different lyssavirus species [13,15]

Methods

Results

Conclusion