An inoculation site-retained mRNA vaccine induces robust immune responses against SARS-CoV-2 variants

文献类型： 外文期刊

第一作者： Huang, Lei

作者： Huang, Lei;Zhao, Fanfan;He, Muye;Fang, Yi;Ma, Xiaoping;Xiao, Hui;Zhu, Hanfei;Wang, Xueli;Tang, Siyuan;Yu, Bo;Wang, Jie;Li, Hangwen;Shen, Haifa;Li, Entao;Gao, Yuwei;Lu, Shuaiyao;Peng, Xiaozhong;Huang, Lei;Zhao, Dong;Wang, Chao

作者机构：

关键词： mRNA vaccine; Inoculation site -retained nanoparticle; COVID-19; SARS-CoV-2

期刊名称：JOURNAL OF CONTROLLED RELEASE （ 影响因子：10.8； 五年影响因子：10.2 ）

ISSN： 0168-3659

年卷期： 2024 年 366 卷

页码：

收录情况： SCI

摘要： mRNA-based vaccines and therapeutic agents hold great promise in prevention and treatment of human diseases, yet high percentage of systemic adverse effect in clinic remains a big safety concern. One major potential cause is a high level of leakage of the locally inoculated mRNA vaccine nanoparticles into circulation. We have screened and optimized a core-shell structured lipopolyplex (LPP) formulation for mRNA with a tissue-retention property. Upon intramuscular inoculation, the mRNA-encapsulated LPP nanoparticles were preferentially taken up by the phagocytic antigen-presentation cells, and potently promoted dendritic cell maturation. We applied the new formulation to prepare a prophylactic vaccine for SARS-CoV-2, and observed potent humoral and cellular immune responses from the vaccine in both murine models and non-human primates. More importantly, the vaccine demonstrated a benign safety profile in non-human primates, with limited side effects after repeated treatment with high dosages of LPP/mRNA. Taken together, the inoculation site-retained vaccine formulation serves as a promising vehicle for mRNA vaccines and therapeutic agents.

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