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.

信使 RNA 疫苗缺乏对树突状细胞 (DC) 的特异性，树突状细胞是抗原呈递最有效的细胞。在这里，我们报告了一种针对 DC 的病毒样颗粒的设计和性能，该颗粒由工程辛德比斯病毒糖蛋白假型化，该糖蛋白可识别 DC 上的表面蛋白，并包装编码严重急性呼吸综合征冠状病毒 2（SARS- CoV-2）或单纯疱疹病毒的糖蛋白 B 和 D 1。在小鼠足垫中注射 DC 靶向 SARS-CoV-2 mRNA 疫苗，可显着提高且持久的抗原特异性免疫球蛋白-G 滴度和细胞免疫反应优于非靶向病毒样颗粒和脂质纳米颗粒制剂。这些疫苗还可以保护小鼠免受 SARS-CoV-2 或单纯疱疹病毒 1 的感染。DC 优先摄取的病毒样颗粒可能有助于开发有效的预防性和治疗性疫苗。