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

Ling Zhong, Wanlin Zhang, Hong Liu, Xinyu Zhang, Zeyu Yang, Zhenfu Wen, Ling Chen, Haolin Chen, Yanran Luo, Yanhong Chen, Qisheng Feng, Mu-Sheng Zeng, Qinjian Zhao, Lixin Liu, Claude Krummenacher (), Yi-Xin Zeng (), Yongming Chen (), Miao Xu () and Xiao Zhang ()
Additional contact information
Ling Zhong: Sun Yat-sen University Cancer Center
Wanlin Zhang: Sun Yat-sen University Cancer Center
Hong Liu: Henan University
Xinyu Zhang: Sun Yat-sen University Cancer Center
Zeyu Yang: Sun Yat-sen University
Zhenfu Wen: Sun Yat-sen University
Ling Chen: Sun Yat-sen University Cancer Center
Haolin Chen: Sun Yat-sen University
Yanran Luo: Sun Yat-sen University Cancer Center
Yanhong Chen: Henan University
Qisheng Feng: Sun Yat-sen University Cancer Center
Mu-Sheng Zeng: Sun Yat-sen University Cancer Center
Qinjian Zhao: Chongqing Medical University
Lixin Liu: Sun Yat-sen University
Claude Krummenacher: Rowan University
Yi-Xin Zeng: Sun Yat-sen University Cancer Center
Yongming Chen: Henan University
Miao Xu: Sun Yat-sen University Cancer Center
Xiao Zhang: Sun Yat-sen University Cancer Center

Nature Communications, 2024, vol. 15, issue 1, 1-21

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-49546-w

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