Sun Cong, Kang Yin-Feng, Fang Xin-Yan, Liu Yi-Na, Bu Guo-Long, Wang Ao-Jie, Li Yan, Zhu Qian-Ying, Zhang Hua, Xie Chu, Kong Xiang-Wei, Peng Yong-Jian, Lin Wen-Jie, Zhou Ling, Chen Xin-Chun, Lu Zheng-Zhou, Xu Hui-Qin, Hong Dong-Chun, Zhang Xiao, Zhong Ling, Feng Guo-Kai, Zeng Yi-Xin, Xu Miao, Zhong Qian, Liu Zheng, Zeng Mu-Sheng
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Experimental Research, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong 510060, China.
Cryo-Electron Microscopy Center, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.
Cell Host Microbe. 2023 Nov 8;31(11):1882-1897.e10. doi: 10.1016/j.chom.2023.09.011. Epub 2023 Oct 16.
Epstein-Barr virus (EBV) is a global public health concern, as it is known to cause multiple diseases while also being etiologically associated with a wide range of epithelial and lymphoid malignancies. Currently, there is no available prophylactic vaccine against EBV. gB is the EBV fusion protein that mediates viral membrane fusion and participates in host recognition, making it critical for EBV infection in both B cells and epithelial cells. Here, we present a gB nanoparticle, gB-I53-50 NP, that displays multiple copies of gB. Compared with the gB trimer, gB-I53-50 NP shows improved structural integrity and stability, as well as enhanced immunogenicity in mice and non-human primate (NHP) preclinical models. Immunization and passive transfer demonstrate a robust and durable protective antibody response that protects humanized mice against lethal EBV challenge. This vaccine candidate demonstrates significant potential in preventing EBV infection, providing a possible platform for developing prophylactic vaccines for EBV.
爱泼斯坦-巴尔病毒(EBV)是一个全球公共卫生问题,因为已知它会引发多种疾病,同时在病因上还与多种上皮和淋巴恶性肿瘤相关。目前,尚无针对EBV的预防性疫苗。gB是EBV融合蛋白,介导病毒膜融合并参与宿主识别,这使其对B细胞和上皮细胞中的EBV感染至关重要。在此,我们展示了一种gB纳米颗粒,即gB-I53-50 NP,它展示了多个拷贝的gB。与gB三聚体相比,gB-I53-50 NP在小鼠和非人类灵长类动物(NHP)临床前模型中显示出改善的结构完整性和稳定性,以及增强的免疫原性。免疫和被动转移证明了强大且持久的保护性抗体反应,可保护人源化小鼠免受致命的EBV攻击。这种候选疫苗在预防EBV感染方面显示出巨大潜力,为开发针对EBV的预防性疫苗提供了一个可能的平台。