Wu Qian, Chen Kaiyun, Xue Wenhui, Wang Guosong, Yang Yanbo, Li Shaowei, Xia Ningshao, Chen Yixin
State Key Laboratory of Vaccines for Infectious Diseases, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Collaborative Innovation Center of Biologic Products, National Innovation Platform for Industry-Education Integration in Vaccine Research, School of Life Sciences, School of Public Health, Xiang An Biomedicine Laboratory, Xiamen University, Xiamen, 361005, China.
Sci China Life Sci. 2025 Mar;68(3):734-745. doi: 10.1007/s11427-023-2599-1. Epub 2024 Oct 31.
Epstein-Barr virus (EBV), the first identified human tumor virus, is implicated in various human malignancies, infectious mononucleosis, and more recently, multiple sclerosis. Prophylactic vaccines have the potential to effectively prevent EBV infection. Glycoprotein B (gB) serves as the fusogen and plays a pivotal role in the virus entry process, making it a critical target for EBV vaccine development. Surface membrane proteins of enveloped viruses serve as native conformational antigens, making them susceptible to immune recognition. Utilizing lipid membrane-bound viral antigens is a promising strategy for effective vaccine presentation in this context. In this study, we employed a truncated design for gB proteins, observing that these truncated gB proteins prompted a substantial release of extracellular vesicles (EVs) in insect cells. We verified that EVs exhibited abundant gB proteins, displaying the typical virus particle morphology and extracellular vesicle characteristics. gB EVs demonstrated a more efficient humoral and cellular immune response compared with the gB ectodomain trimer vaccine in mice. Moreover, the antisera induced by the gB EVs vaccine exhibited robust antibody-dependent cytotoxicity. Consequently, gB EVs-based vaccines hold significant potential for preventing EBV infection and offer valuable insights for vaccine design.
爱泼斯坦-巴尔病毒（EBV）是首个被鉴定出的人类肿瘤病毒，与多种人类恶性肿瘤、传染性单核细胞增多症以及最近发现的多发性硬化症有关。预防性疫苗有潜力有效预防EBV感染。糖蛋白B（gB）作为融合蛋白，在病毒进入过程中起关键作用，使其成为EBV疫苗开发的关键靶点。包膜病毒的表面膜蛋白作为天然构象抗原，易被免疫识别。在这种情况下，利用脂质膜结合的病毒抗原是有效呈现疫苗的一种有前景的策略。在本研究中，我们对gB蛋白采用了截短设计，观察到这些截短的gB蛋白促使昆虫细胞大量释放细胞外囊泡（EVs）。我们证实EVs展示出丰富的gB蛋白，呈现出典型的病毒颗粒形态和细胞外囊泡特征。与gB胞外结构域三聚体疫苗相比，gB EVs在小鼠中表现出更有效的体液免疫和细胞免疫反应。此外，gB EVs疫苗诱导的抗血清表现出强大的抗体依赖性细胞毒性。因此，基于gB EVs的疫苗在预防EBV感染方面具有巨大潜力，并为疫苗设计提供了有价值的见解。
