A safe and broad-spectrum SARS-CoV-2 mRNA vaccine with a new delivery system for <em>in-situ</em> expression

Weiyi Yu; Xianying Chen; Qiubing Chen; Peixuan Chen; Naizhang Liu; Yingjian Li; Xue Tan; Qiuhan Zhang; Yan Rao; Ming Guo; Zhixiang Huang; Xin Wang; Zhen Zhang; Wenjie Xiang; Yuzhen Zhang; Qianyun Liu; Hao Yin; Li Zhou; Yu Chen; Ke Lan

doi:10.1016/j.virs.2025.09.001

October 2025

Citation: Weiyi Yu, Xianying Chen, Qiubing Chen, Peixuan Chen, Naizhang Liu, Yingjian Li, Xue Tan, Qiuhan Zhang, Yan Rao, Ming Guo, Zhixiang Huang, Xin Wang, Zhen Zhang, Wenjie Xiang, Yuzhen Zhang, Qianyun Liu, Hao Yin, Li Zhou, Yu Chen, Ke Lan. A safe and broad-spectrum SARS-CoV-2 mRNA vaccine with a new delivery system for in-situ expression .VIROLOGICA SINICA, 2025, 40(5) : 793-803. http://dx.doi.org/10.1016/j.virs.2025.09.001

A safe and broad-spectrum SARS-CoV-2 mRNA vaccine with a new delivery system for in-situ expression

Weiyi Yu ^a ,
Xianying Chen ^b ,
Qiubing Chen ^c ,
Peixuan Chen ^a ,
Naizhang Liu ^a ,
Yingjian Li ^a ,
Xue Tan ^a ,
Qiuhan Zhang ^d ,
Yan Rao ^b ,
Ming Guo ^a ,
Zhixiang Huang ^b ,
Xin Wang ^a ,
Zhen Zhang ^b ,
Wenjie Xiang ^a ,
Yuzhen Zhang ^a ,
Qianyun Liu ^a ,
Hao Yin ^c,e ,
Li Zhou ^{b
,,} ,
Yu Chen ^{a
,,} ,
Ke Lan ^{a,b,d,e
,,}

a. State Key Laboratory of Virology and Biosafety, RNA Institute, College of Life Sciences, Wuhan University, Wuhan, 430072, China;
b. Institute for Vaccine Research at Animal Bio-safety Level Ⅲ Laboratory, Wuhan University, Wuhan, 430071, China;
c. Departments of Urology and Laboratory Medicine, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, 430071, China;
d. Department of Infectious Diseases, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China;
e. Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan 430071, China

Corresponding author: Li Zhou, zhouli_jerry@whu.edu.cn
Yu Chen, chenyu@whu.edu.cn
Ke Lan, klan@whu.edu.cn
Received Date: 09 June 2025
Accepted Date: 01 September 2025
Available online: 04 September 2025

Abstract

Since the outbreak of COVID-19 in late 2019, the cumulative number of confirmed cases worldwide has surpassed 778 million, and the number of deaths has exceeded 7 million, posing a significant threat to human life and health while inflicting enormous losses on the global economy. At the stage where sequential immunization is recommended, there is a pressing demand for mRNA vaccines that can be rapidly adapted to new sequences, are easy to industrialize, and exhibit high safety and effectiveness. We developed a lipid nanoparticle (LNP) system, designated as WNP, which facilitates essentially in situ expression at the injection site and results in lower levels of pro-inflammatory factors in the liver, thus enhancing its safety compared to liver-targeted alternatives. Furthermore, in light of the swiftly mutating characteristic of SARS-CoV-2, a study has used cross-lineage chimeras and mutation patch strategies to design an antigen that is highly immunogenic and can stimulate the production of a broad range of effective antibodies. Therefore, we used the same antigenic configuration of RBD including five key mutation sites (K417T, L452R, T478K, E484K, and N501Y) to achieve optimal broad-spectrum efficacy. Our results indicate that WNP can elicit a humoral immunity response that is as robust as that of SM-102, a stronger cellular immune response, and provide a certain protective effect. On top of that, WNP can be applied to the development of vaccines targeting other pathogens and will contribute to a quicker response to the spillovers of unknown mammalian viruses.
- SARS-CoV-2
- , mRNA vaccine
- , Lipid nanoparticles

Electronic Supplementary Material

10.1016j.virs.2025.09.001-ESM1.docx
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