Bovine Respiratory Syncitial Virus Vaccine (360G-Wellcome-207180_Z_17_Z)

Bovine respiratory syncitial virus (BRSV) is a leading cause of enzootic pneumonia in calves and significantly contributes to the Bovine Respiratory Disease Complex found in feedlot cattle. It is proposed to develop a new vaccine using the Semliki Forest Virus (SFV) virus replicon particle (VRP) vaccine platform. The SFV VRP is a promising vaccine platform, due in part to its efficacious immunogenicity in cattle and its ability to express protein to high concentrations in the cells it infects. Furthermore, the replicon vectors are single cycle, propagation-defective particles that are not able to spread beyond the initial infected cells. The BRSV fusion (F) protein is known to be immunogenic thus making it a good candidate protein to target for gene expression. It is proposed to clone the F protein sequence into a VRP expression plasmid in place of the SFV structural proteins. The proposed project will involve generating the VRP plasmids, generation of VRP stocks and confirmation that this VRP can express the F protein. Human respiratory syncitial virus (hRSV), a closely related virus of human importance, also expresses the F protein. Thus BRSV infection in bovines is a relevant model for hRSV, as there is no current efficacious vaccine available.