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A potent and protective human neutralizing antibody targeting a novel vulnerable site of Epstein-Barr virus

Author

Listed:
  • Qian-Ying Zhu

    (Sun Yat-sen University Cancer Center (SYSUCC)
    Sun Yat-sen University)

  • Sisi Shan

    (Tsinghua University)

  • Jinfang Yu

    (Tsinghua University)

  • Si-Ying Peng

    (Bejing IDMO Company Limited)

  • Cong Sun

    (Sun Yat-sen University Cancer Center (SYSUCC))

  • Yanan Zuo

    (Tsinghua University)

  • Lan-Yi Zhong

    (Sun Yat-sen University Cancer Center (SYSUCC))

  • Shu-Mei Yan

    (Sun Yat-sen University Cancer Center (SYSUCC))

  • Xiao Zhang

    (Sun Yat-sen University Cancer Center (SYSUCC))

  • Ziqing Yang

    (Tsinghua University)

  • Yong-Jian Peng

    (Sun Yat-sen University Cancer Center (SYSUCC))

  • Xuanling Shi

    (Tsinghua University)

  • Su-Mei Cao

    (Sun Yat-sen University Cancer Center (SYSUCC))

  • Xinquan Wang

    (Tsinghua University)

  • Mu-Sheng Zeng

    (Sun Yat-sen University Cancer Center (SYSUCC))

  • Linqi Zhang

    (Tsinghua University
    Tsinghua University
    Shenzhen Bay Laboratory)

Abstract

Epstein-Barr virus (EBV) is associated with a range of epithelial and B cell malignancies as well as autoimmune disorders, for which there are still no specific treatments or effective vaccines. Here, we isolate EBV gH/gL-specific antibodies from an EBV-infected individual. One antibody, 1D8, efficiently neutralizes EBV infection of two major target cell types, B cells and epithelial cells. In humanized mice, 1D8 provides protection against a high-dose EBV challenge by substantially reducing viral loads and associated tumor burden. Crystal structure analysis reveals that 1D8 binds to a key vulnerable interface between the D-I/D-II domains of the viral gH/gL protein, especially the D-II of the gH, thereby interfering with the gH/gL-mediated membrane fusion and binding to target cells. Overall, we identify a potent and protective neutralizing antibody capable of reducing the EBV load. The novel vulnerable site represents an attractive target that is potentially important for antibody and vaccine intervention against EBV infection.

Suggested Citation

  • Qian-Ying Zhu & Sisi Shan & Jinfang Yu & Si-Ying Peng & Cong Sun & Yanan Zuo & Lan-Yi Zhong & Shu-Mei Yan & Xiao Zhang & Ziqing Yang & Yong-Jian Peng & Xuanling Shi & Su-Mei Cao & Xinquan Wang & Mu-Sh, 2021. "A potent and protective human neutralizing antibody targeting a novel vulnerable site of Epstein-Barr virus," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26912-6
    DOI: 10.1038/s41467-021-26912-6
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    References listed on IDEAS

    as
    1. Polterovich, Victor & Popov, Vladimir, 2006. "Эволюционная Теория Экономической Политики: Часть I: Опыт Быстрого Развития [An Evolutionary Theory of Economic Policy: Part I: The Experience of Fast Development]," MPRA Paper 22168, University Library of Munich, Germany.
    2. Karthik Sathiyamoorthy & Yao Xiong Hu & Britta S. Möhl & Jia Chen & Richard Longnecker & Theodore S. Jardetzky, 2016. "Structural basis for Epstein–Barr virus host cell tropism mediated by gp42 and gHgL entry glycoproteins," Nature Communications, Nature, vol. 7(1), pages 1-14, December.
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    Cited by:

    1. Yang Liu & Shuang-Yan Ye & Shuai He & Dong-Mei Chi & Xiu-Zhi Wang & Yue-Feng Wen & Dong Ma & Run-Cong Nie & Pu Xiang & You Zhou & Zhao-Hui Ruan & Rou-Jun Peng & Chun-Ling Luo & Pan-Pan Wei & Guo-Wang , 2024. "Single-cell and spatial transcriptome analyses reveal tertiary lymphoid structures linked to tumour progression and immunotherapy response in nasopharyngeal carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-22, December.

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