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

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.

• Authors: 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, Linqi Zhang
• Journal: Nature communications (Nat Commun) Vol. 12 Issue 1 Pg. 6624 (11 16 2021) ISSN: 2041-1723 [Electronic] England
• PMID: 34785638 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s).

Chemical References

• Antibodies, Neutralizing
• Antibodies, Viral
• Astn2 protein, mouse
• Epitopes
• Glycoproteins
• Nerve Tissue Proteins
• Viral Proteins

Topics

• Animals
• Antibodies, Neutralizing (chemistry, immunology)
• Antibodies, Viral (immunology)
• B-Lymphocytes (immunology)
• Crystallography, X-Ray
• Epithelial Cells (immunology)
• Epitopes
• Epstein-Barr Virus Infections (immunology, virology)
• Glycoproteins (chemistry)
• Herpesvirus 4, Human (immunology)
• Humans
• Membrane Fusion
• Mice
• Nerve Tissue Proteins (chemistry)
• Viral Proteins (metabolism)
• Virus Replication