DPhil in Clinical Medicine: New approaches to vaccine development against Epstein Barr Virus and Rabies

The role of the viral Membrane Fusion Protein (MFP) is to force the lipid bilayer of the virus membrane into close enough proximity to that of the host cell that they merge, facilitating entry of the virus. This fusion relies on significant conformational changes in the MFP, from a pre-fusion to a post-fusion conformation, to overcome the energetic penalty associated with the similarly-charged membranes being brought together. It might therefore be possible to prevent viral entry into the cell by inhibiting the action of the MFPs, either by blocking binding to its relevant host cell receptor, or trapping it in the pre-fusion conformation. This project aims to elucidate how the pre-fusion and post-fusion structures of two MFPs, Rabies Virus Glycoprotein and Epstein Barr Virus glycoprotein B, might be manipulated for use in vaccine development against these two viruses. By promoting the generation of antibodies that recognise these MFPs, such vaccines might elicit protection against cell entry of the virus and therefore against disease.