Dendritic-cell-targeting Virus-like Particles As Potent MRNA Vaccine Carriers

Nature biomedical engineering  ·  2024  ·  Impact 4

Di Yin; Yiye Zhong; Sikai Ling; Sicong Lu; Xiaoyuan Wang; Zhuofan Jiang; Jie Wang; Yao Dai; Xiaolong Tian; Qijing Huang; Xingbo Wang; Junsong Chen; Ziying Li; Yang Li; Zhijue Xu; Hewei Jiang; Yuqing Wu; Yi Shi; Quanjun Wang; Jianjiang Xu; Wei Hong; Heng Xue; Hang Yang; Yan Zhang; Lintai Da; Ze-Guang Han; Sheng-Ce Tao; Ruijiao Dong; Tianlei Ying; Jiaxu Hong; Yujia Cai;

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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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