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

文献类型: 外文期刊

作者: Huang, Lei 1 ; Zhao, Fanfan 1 ; He, Muye 1 ; Fang, Yi 1 ; Ma, Xiaoping 1 ; Lu, Shuaiyao 3 ; Li, Entao 2 ; Xiao, Hui 1 ; Zhu, Hanfei 1 ; Wang, Xueli 1 ; Tang, Siyuan 1 ; Yu, Bo 1 ; Wang, Jie 1 ; Zhao, Dong 4 ; Wang, Chao 4 ; Li, Hangwen 1 ; Gao, Yuwei 2 ; Peng, Xiaozhong 3 ; Shen, Haifa 1 ;

作者机构: 1.Stemirna Therapeut, Shanghai 201206, Peoples R China

2.Chinese Acad Agr Sci, Changchun Vet Res Inst, Changchun 130122, Peoples R China

3.Chinese Acad Med Sci & Peking Union Med Coll, Inst Med Biol, Yunnan Key Lab Vaccine Res & Dev Severe Infect Dis, Kunming 650118, Peoples R China

4.Fudan Univ, Dept Mat Sci, Shanghai 200433, Peoples R China

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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