State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Cryo-electron Microscopy Center, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China; Department of Chemical Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.
Cell Rep Med. 2024 May 21;5(5):101573. doi: 10.1016/j.xcrm.2024.101573.
Epstein-Barr virus (EBV) is linked to various malignancies and autoimmune diseases, posing a significant global health challenge due to the lack of specific treatments or vaccines. Despite its crucial role in EBV infection in B cells, the mechanisms of the glycoprotein gp42 remain elusive. In this study, we construct an antibody phage library from 100 EBV-positive individuals, leading to the identification of two human monoclonal antibodies, 2B7 and 2C1. These antibodies effectively neutralize EBV infection in vitro and in vivo while preserving gp42's interaction with the human leukocyte antigen class II (HLA-II) receptor. Structural analysis unveils their distinct binding epitopes on gp42, different from the HLA-II binding site. Furthermore, both 2B7 and 2C1 demonstrate potent neutralization of EBV infection in HLA-II-positive epithelial cells, expanding our understanding of gp42's role. Overall, this study introduces two human anti-gp42 antibodies with potential implications for developing EBV vaccines targeting gp42 epitopes, addressing a critical gap in EBV research.
EB 病毒（EBV）与多种恶性肿瘤和自身免疫性疾病有关，由于缺乏特定的治疗方法或疫苗，因此对全球健康构成了重大挑战。尽管糖蛋白 gp42 在 EBV 感染 B 细胞中起着至关重要的作用，但它的作用机制仍不清楚。在这项研究中，我们从 100 名 EBV 阳性个体中构建了一个抗体噬菌体文库，从而鉴定出两种人类单克隆抗体，2B7 和 2C1。这些抗体可有效中和 EBV 的体外和体内感染，同时保持 gp42 与人白细胞抗原 II 类（HLA-II）受体的相互作用。结构分析揭示了它们在 gp42 上的独特结合表位，与 HLA-II 结合位点不同。此外，2B7 和 2C1 均能有效中和 HLA-II 阳性上皮细胞中的 EBV 感染，从而扩展了我们对 gp42 作用的认识。总的来说，这项研究介绍了两种具有潜在意义的人类抗 gp42 抗体，可用于开发针对 gp42 表位的 EBV 疫苗，填补了 EBV 研究中的一个关键空白。
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