Investigating antigenic epitopes on the lyssavirus glycoprotein

The lyssaviruses are a group of important zoonotic pathogens of considerable risk to both public and animal health and include rabies virus. Rabies virus currently causes >50,000 deaths/year across the developing world although the impact of non-rabies lyssaviruses remains unclear. Antigenically, lyssaviruses are currently characterised into three phylogroups based on studies detailing vaccination/challenge experimentation. All current rabies vaccines are based on passage attenuated rabies isolates belonging to phylogroup I. The serological response following vaccination with the current vaccines have been shown experimentally to provide no protection against viruses from phylogroups II and III. A crystal structure for the lyssavirus G protein is not currently available although five antigenic domains have been described and their roles in neutralisation by different monoclonal antibodies studied. Here we present data analysing the importance of the different antigenic sites for virus neutralisation using the pseudotype assay (Wright et al, 2008). Initially we have exchanged the antigenic sites between a phylogroup I and a phylogroup II isolate, and vice versa, to study the effect on pseudotype neutralisation by rabies hyperimmune sera.