A cocktail nanovaccine targeting key entry glycoproteins elicits high neutralizing antibody levels against EBV infection

作者全名：Zhong, Ling; Zhang, Wanlin; Liu, Hong; Zhang, Xinyu; Yang, Zeyu; Wen, Zhenfu; Chen, Ling; Chen, Haolin; Luo, Yanran; Chen, Yanhong; Feng, Qisheng; Zeng, Mu-Sheng; Zhao, Qinjian; Liu, Lixin; Krummenacher, Claude; Zeng, Yi-Xin; Chen, Yongming; Xu, Miao; Zhang, Xiao

作者地址：[Zhong, Ling; Zhang, Wanlin; Zhang, Xinyu; Chen, Ling; Luo, Yanran; Feng, Qisheng; Zeng, Mu-Sheng; Zeng, Yi-Xin; Xu, Miao; Zhang, Xiao] Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China, Guangdong Key Lab Nasopharyngeal Carcinoma Diag &, Guangzhou 510060, Peoples R China; [Liu, Hong; Chen, Yanhong] Henan Univ, Huaihe Hosp, Translat Med Ctr, Kaifeng 475004, Peoples R China; [Yang, Zeyu; Wen, Zhenfu; Chen, Haolin; Liu, Lixin] Sun Yat Sen Univ, Ctr Funct Biomat, Sch Mat Sci & Engn, Key Lab Polymer Composite & Funct Mat,Minist Educ, Guangzhou, Peoples R China; [Zhao, Qinjian; Zhang, Xiao] Chongqing Med Univ, Coll Pharm, Chongqing, Peoples R China; [Krummenacher, Claude] Rowan Univ, Dept Biol & Biomed Sci, Glassboro, NJ 08028 USA; [Chen, Yongming] Henan Univ, Coll Chem & Mol Sci, Zhengzhou 450046, Peoples R China

通信作者：Zeng, YX; Xu, M; Zhang, X (通讯作者)，Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China, Guangdong Key Lab Nasopharyngeal Carcinoma Diag &, Guangzhou 510060, 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.; Chen, YM (通讯作者)，Henan Univ, Coll Chem & Mol Sci, Zhengzhou 450046, Peoples R China.

来源：NATURE COMMUNICATIONS

ESI学科分类：　

WOS号：WOS:001252409000003

JCR分区：Q1

影响因子：14.7

年份：2024

卷号：15

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要：Epstein-Barr virus (EBV) infects more than 95% of adults worldwide and is closely associated with various malignancies. Considering the complex life cycle of EBV, developing vaccines targeting key entry glycoproteins to elicit robust and durable adaptive immune responses may provide better protection. EBV gHgL-, gB- and gp42-specific antibodies in healthy EBV carriers contributed to sera neutralizing abilities in vitro, indicating that they are potential antigen candidates. To enhance the immunogenicity of these antigens, we formulate three nanovaccines by co-delivering molecular adjuvants (CpG and MPLA) and antigens (gHgL, gB or gp42). These nanovaccines induce robust humoral and cellular responses through efficient activation of dendritic cells and germinal center response. Importantly, these nanovaccines generate high levels of neutralizing antibodies recognizing vulnerable sites of all three antigens. IgGs induced by a cocktail vaccine containing three nanovaccines confer superior protection from lethal EBV challenge in female humanized mice compared to IgG elicited by individual NP-gHgL, NP-gB and NP-gp42. Importantly, serum antibodies elicited by cocktail nanovaccine immunization confer durable protection against EBV-associated lymphoma. Overall, the cocktail nanovaccine shows robust immunogenicity and is a promising candidate for further clinical trials. In this study, the authors show that nanovaccines co-delivering EBV antigens and molecular adjuvants generate high levels of neutralizing antibodies targeting vulnerable EBV sites of gHgL, gB and gp42. Antibodies elicited by cocktail nanovaccine immunization provide durable protection against EBV-associated lymphoma.

基金机构：National Natural Science Foundation of China (National Science Foundation of China) [2022YFC2305400]; National Key Research and Development Program of China [82371832, 82122050, 82341037, 22075324]; National Natural Science Foundation of China [2023J011235]; Natural Science Foundation of Fujian Province [KJQN202300453]; Chongqing Education Commission of Science and Technology Research Project [2023NSCQ-MSX1536]; Natural Science Foundation of Chongqing City

基金资助正文：This work was supported by the grant from the National Key Research and Development Program of China Grant (2022YFC2305400 to M.X.); National Natural Science Foundation of China Grant (82371832 to Xiao.Zhang., 82122050 to M.X., 82341037 to Yong.Chen. and 22075324 to L.L); Natural Science Foundation of Fujian Province (2023J011235 to Xiao.Zhang.); Chongqing Education Commission of Science and Technology Research Project (KJQN202300453 to Xiao.Zhang.); Natural Science Foundation of Chongqing City (2023NSCQ-MSX1536 to Xiao. Zhang).