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

临床医学博士：开发针对 Epstein Barr 病毒和狂犬病疫苗的新方法

• 批准号: 2436253
• 金额: --
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2436253
• 关键词: DPhil; Clinical; Medicine; New; approaches

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.

病毒膜融合蛋白(MFP)的作用是迫使病毒膜的脂双层与宿主细胞的脂双层足够接近，从而使它们融合，促进病毒的进入。这种融合依赖于MFP中显著的构象变化，从融合前的构象到融合后的构象，以克服与相似带电的膜聚集在一起相关的能量惩罚。因此，有可能通过抑制MFP的作用来阻止病毒进入细胞，方法是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。本项目旨在阐明狂犬病病毒糖蛋白和Epstein Barr病毒糖蛋白B这两个MFP融合前和融合后的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，这种疫苗可能会产生保护，防止病毒进入细胞，从而抵御疾病。

项目成果

Structure of trimeric pre-fusion rabies virus glycoprotein in complex with two protective antibodies

狂犬病病毒融合前三聚体糖蛋白与两种保护性抗体复合物的结构

• DOI: 10.1101/2022.02.28.482293
• 发表时间: 2022
• 作者: Ng W