Neutralizing antibodies against EBV gp42 show potent in vivo protection and define novel epitopes

Qian Wu, Ling Zhong, Dongmei Wei, Wanlin Zhang, Junping Hong, Yinfeng Kang, Kaiyun Chen, Yang Huang, Qingbing Zheng, Miao Xu, Mu Sheng Zeng, Yi Xin Zeng, Ningshao Xia, Qinjian Zhao, Claude Krummenacher, Yixin Chen, Xiao Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number2245920
JournalEmerging Microbes and Infections
Volume12
Issue number2
DOIs
StatePublished - 2023

All Science Journal Classification (ASJC) codes

  • Epidemiology
  • Parasitology
  • Microbiology
  • Immunology
  • Drug Discovery
  • Infectious Diseases
  • Virology

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