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. 2025 Feb;9(2):185-200.
doi: 10.1038/s41551-024-01208-4. Epub 2024 May 7.

Dendritic-cell-targeting virus-like particles as potent mRNA vaccine carriers

Di Yin #  1 , Yiye Zhong #  1 , Sikai Ling #  1   2 , Sicong Lu #  1 , Xiaoyuan Wang #  2 , Zhuofan Jiang  1 , Jie Wang  1 , Yao Dai  1 , Xiaolong Tian  3 , Qijing Huang  1 , Xingbo Wang  4 , Junsong Chen  1 , Ziying Li  1 , Yang Li  1 , Zhijue Xu  1 , Hewei Jiang  1 , Yuqing Wu  5 , Yi Shi  6 , Quanjun Wang  7 , Jianjiang Xu  5 , Wei Hong  8   9 , Heng Xue  8   9 , Hang Yang  8   9   10 , Yan Zhang  1 , Lintai Da  1 , Ze-Guang Han  1 , Sheng-Ce Tao  1 , Ruijiao Dong  1 , Tianlei Ying  3 , Jiaxu Hong  11 , Yujia Cai  12
Affiliations

Dendritic-cell-targeting virus-like particles as potent mRNA vaccine carriers

Di Yin et al. Nat Biomed Eng. 2025 Feb.

Abstract

Messenger RNA vaccines lack specificity for dendritic cells (DCs)-the most effective cells at antigen presentation. Here we report the design and performance of a DC-targeting virus-like particle pseudotyped with an engineered Sindbis-virus glycoprotein that recognizes a surface protein on DCs, and packaging mRNA encoding for the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or for the glycoproteins B and D of herpes simplex virus 1. Injection of the DC-targeting SARS-CoV-2 mRNA vaccine in the footpad of mice led to substantially higher and durable antigen-specific immunoglobulin-G titres and cellular immune responses than untargeted virus-like particles and lipid-nanoparticle formulations. The vaccines also protected the mice from infection with SARS-CoV-2 or with herpes simplex virus 1. Virus-like particles with preferential uptake by DCs may facilitate the development of potent prophylactic and therapeutic vaccines.

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Conflict of interest statement

Competing interests: Y.C. is a co-founder and advisor of BDGENE Therapeutics. The other authors declare no competing interests.

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