Rabies is a lethal zoonotic infectious disease. Vaccines against the rabies virus have significantly reduced the number of deaths from the disease. However, all the licensed rabies vaccines are inactivated vaccines, which have limited immunogenicity and complicated immunization procedures. A novel vaccine that provides sustained and comprehensive protection is urgently needed. Here, we developed a novel rabies mRNA vaccine candidate containing sequence-optimized mRNAs encoding full-length glycoprotein encapsulated in ionizable lipid nanoparticles. In mice and rhesus macaques, the rabies mRNA exhibited superior immunogenicity over licensed vaccines, especially in inducing long-lasting neutralizing antibodies and memory B cells. A single administration of 1.5 μg mRNA vaccine could provide complete protection against a lethal rabies virus challenge in mice. Additionally, the mRNA vaccine could robustly activate cellular immune responses with moderate release of several cytokines. In summary, our data demonstrated that the rabies mRNA vaccine outperformed approved inactivated vaccines in both mice and rhesus macaques. This highlights the potential of the mRNA platform in developing next-generation rabies vaccines.

中文翻译：

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核苷修饰的狂犬病 mRNA 疫苗可在小鼠和非人灵长类动物中诱导持久而全面的免疫反应。


狂犬病是一种致命的人畜共患传染病。针对狂犬病病毒的疫苗显著减少了死于该病的人数。然而，所有获得许可的狂犬病疫苗都是灭活疫苗，免疫原性有限，免疫程序复杂。迫切需要一种提供持续和全面保护的新型疫苗。在这里，我们开发了一种新型狂犬病 mRNA 候选疫苗，其中包含编码封装在可电离脂质纳米颗粒中的全长糖蛋白的序列优化 mRNA。在小鼠和恒河猴中，狂犬病 mRNA 表现出优于许可疫苗的免疫原性，尤其是在诱导长效中和抗体和记忆 B 细胞方面。单次接种 1.5 μg mRNA 疫苗可以完全保护小鼠免受致命的狂犬病病毒攻击。此外，mRNA 疫苗可以通过适度释放多种细胞因子来稳健地激活细胞免疫反应。总之，我们的数据表明，狂犬病 mRNA 疫苗在小鼠和恒河猴中的表现优于已批准的灭活疫苗。这凸显了 mRNA 平台在开发下一代狂犬病疫苗方面的潜力。