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

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

作者地址："[Wu, Qian; Wei, Dongmei; Hong, Junping; Chen, Kaiyun; Huang, Yang; Zheng, Qingbing; Xia, Ningshao; Chen, Yixin] Xiamen Univ, Natl Inst Diagnost & Vaccine Dev Infect Dis, Collaborat Innovat Ctr Biol Prod, Sch Life Sci,State Key Lab Vaccines Infect Dis,Nat, Xiamen, Peoples R China; [Zhong, Ling; Zhao, Qinjian; Zhang, Xiao] Chongqing Med Univ, Coll Pharm, Chongqing, Peoples R China; [Zhong, Ling; Zhang, Wanlin; Kang, Yinfeng; Xu, Miao; Zeng, Mu-Sheng; Zeng, Yi-Xin] Sun Yat Sen Univ, Canc Ctr, Collaborat Innovat Ctr Canc Med, Dept Expt Res,State Key Lab Oncol South China, Guangzhou, Peoples R China; [Krummenacher, Claude] Rowan Univ, Dept Biol & Biomed Sci, Glassboro, NJ 08028 USA"

通信作者："Chen, YX (通讯作者)，Xiamen Univ, Natl Inst Diagnost & Vaccine Dev Infect Dis, Collaborat Innovat Ctr Biol Prod, Sch Life Sci,State Key Lab Vaccines Infect Dis,Nat, Xiamen, Peoples R China.; Zhang, X (通讯作者)，Chongqing Med Univ, Coll Pharm, Chongqing, Peoples R China.; Krummenacher, C (通讯作者)，Rowan Univ, Dept Biol & Biomed Sci, Glassboro, NJ 08028 USA."

来源：EMERGING MICROBES & INFECTIONS

ESI学科分类：MICROBIOLOGY

WOS号：WOS:001050276700001

JCR分区：Q1

影响因子：8.4

年份：2023

卷号：12

期号：2

开始页：　

结束页：　

文献类型：Article

关键词：Epstein-Barr virus; glycoprotein gp42; neutralizing antibody; humanized mouse model; membrane fusion; lymphoma; >

摘要："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."

基金机构："National Natural Science Foundation of China [82073756, 32170942, 81991491, 81702001, 32070925]; Chongqing Education Commission of Science and Technology Research Project [KJQN202300453]; Natural Science Foundation of Chongqing City [2023NSCQ-MSX1536]; Natural Science Foundation of Fujian Province [2023J011235]"

基金资助正文："This work was supported by grants from the National Natural Science Foundation of China [82073756 to Y.C, 32170942 and 81991491 to Q.B.Z, 81702001 to X.Z., 32070925 to Q.Zhao]; Chongqing Education Commission of Science and Technology Research Project (KJQN202300453); Natural Science Foundation of Chongqing City [2023NSCQ-MSX1536 to X.Z.]; Natural Science Foundation of Fujian Province [2023J011235 to X.Z.]."