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

病毒膜融合蛋白（MFP）的作用是迫使病毒膜的脂质双层与宿主细胞的脂质双层足够接近，使它们融合，促进病毒的进入。这种融合依赖于MFP中从融合前构象到融合后构象的显著构象变化，以克服与带相似电荷的膜聚集在一起相关的能量损失。因此，有可能通过阻断与其相关宿主细胞受体的结合或将其捕获在融合前构象中来抑制MFP的作用，从而防止病毒进入细胞。本项目旨在阐明狂犬病病毒糖蛋白和爱泼斯坦巴尔病毒糖蛋白B这两种MFP的融合前和融合后结构如何被操纵以用于针对这两种病毒的疫苗开发。通过促进识别这些MFP的抗体的产生，这种疫苗可能会引起对病毒进入细胞的保护，从而对抗疾病。

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.