爱泼斯坦—巴尔病毒（EBV）是首个报道的影响人体的致肿瘤病毒，全球人口中超过95%被感染。EBV在B淋巴细胞中的潜伏感染对病毒的持续性至关重要。糖蛋白gp42是EBV进入B细胞的触发复合物中不可或缺的成员。gp42的C型凝集素结构域（CTLD）在受体结合中起着关键作用，并是中和抗体的主要靶标。在本研究中，我们分离出两种具有强力中和B细胞感染活性的兔抗体1A7和6G7，针对gp42的CTLD。抗体6G7能够有效地保护人源化小鼠免受致命性EBV挑战和EBV诱导的淋巴瘤。抗体1A7和6G7靶向的中和表位是独特且新颖的。抗体6G7能够阻断gp42与B细胞表面的结合，而1A7和6G7均可抑制与B细胞的膜融合。此外，免疫血清中的1A7和6G7样抗体是对B细胞中和的主要贡献因子。本研究表明，针对gp42的中和抗体对抑制EBV感染是有效的，并为基于gp42的疫苗和治疗药物的设计提供了新的启示。

Epstein-Barr virus (EBV) is the first reported human oncogenic virus and infects more than 95% of the human population worldwide. EBV latent infection in B lymphocytes is essential for viral persistence. Glycoprotein gp42 is an indispensable member of the triggering complex for EBV entry into B cells. The C-type lectin domain (CTLD) of gp42 plays a key role in receptor binding and is the major target of neutralizing antibodies. Here, we isolated two rabbit antibodies, 1A7 and 6G7, targeting gp42 CTLD with potent neutralizing activity against B cell infection. Antibody 6G7 efficiently protects humanized mice from lethal EBV challenge and EBV-induced lymphoma. Neutralizing epitopes targeted by antibodies 1A7 and 6G7 are distinct and novel. Antibody 6G7 blocks gp42 binding to B cell surface and both 1A7 and 6G7 inhibit membrane fusion with B cells. Furthermore, 1A7- and 6G7-like antibodies in immunized sera are major contributors to B cell neutralization. This study demonstrates that anti-gp42 neutralizing antibodies are effective in inhibiting EBV infection and sheds light on the design of gp42-based vaccines and therapeutics.