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

作者：L. Zhong, Wanlin Zhang, Hong Liu, Xinyu Zhang, Xinyu Zhang, Zeyu Yang, Zhenfu Wen, Ling Chen, Haolin Chen, Yanran Luo, Yanhong Chen, Yanhong Chen, Qi‐Sheng Feng, Mu‐Sheng Zeng, Qinjian Zhao, Lixin Liu, Claude Krummenacher, Yi‐Xin Zeng, Yongming Chen, Yongming Chen, Miao Xu, Xiao Zhang, Xiao Zhang · 发表于：Nature Communications · 年份：2024 · DOI：10.1038/s41467-024-49546-w · 被引用次数：26 · 研究领域：Herpesvirus Infections and Treatments、Virology and Viral Diseases、Animal Virus Infections Studies

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.