Generation of Arctic-like Rabies Viruses Containing Chimeric Glycoproteins Enables Serological Potency Studies.

Abstract

Rabies viruses have the highest case fatality rate of any known virus and are responsible for an estimated 60,000 deaths each year. This is despite the fact that there are highly efficacious vaccines and postexposure prophylaxis available. However, while it is assumed these biologics provide protection against all rabies virus isolates, there are certain subdivisions of RABV lineages, such as within the Arctic-like RABV (AL rabies virus lineage, where data is limited and thus the potency of existing biologics has not been thoroughly assessed. By fusing the Arctic-like rabies virus envelope glycoprotein ecto- and transmembrane domains with the vesicular stomatitis virus cytoplasmic domain, a high titre (7.7 x 105 - 6.1 x 106 RLU/ml) pseudotyped virus was generated that was subsequently used in a pseudotyped virus neutralisation assay. These results showed that Arctic-like rabies viruses are neutralised to human, canine and feline vaccines and human post-exposure prophylaxis and this was not influenced by the swapping of the cytoplasmic domains (CVS-11 vs CVS-11etmVSVc; r = 0.99, p < 0.0001). This study supports the concept that rabies virus vaccines and newly identified mAbs are able to neutralise rabies virus variants that cluster in a monophyletic clade, referred to as phylogroup I lyssaviruses.