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

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-Sheng Zeng () and Linqi Zhang ()
Additional contact information
Qian-Ying Zhu: Sun Yat-sen University Cancer Center (SYSUCC)
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

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26912-6

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DOI: 10.1038/s41467-021-26912-6

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