Wang Yu, Yu Tingting, Zhang Shoufeng, Li Nan, Zhao Jinghui, Mi Lijuan, Cai Yanan, Yao Naiquan, Hu Rongliang, Miao Faming
State Key Laboratory of Pathogen and Biosecurity, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, PR China; College of Veterinary Medicine, Jilin Agricultural University, Changchun, PR China.
State Key Laboratory of Pathogen and Biosecurity, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, PR China.
Vet Microbiol. 2025 Aug;307:110612. doi: 10.1016/j.vetmic.2025.110612. Epub 2025 Jun 27.
Rabies is a zoonotic disease caused by the rabies virus (RABV). RABV infections cause severe destruction to the central nervous system with fatal consequences, which has prompted global efforts to develop a highly effective and safe vaccine. Currently, the most widely used vaccines are inactivated vaccines, which need multiple injected doses for either pre-exposure prophylaxis or post-exposure immunization. This adds a lot of unnecessary trouble and labor costs. mRNA vaccines represent a promising platform against emerging and re-emerging infectious diseases, because they can induce high levels of virus-neutralizing antibodies (VNAs). In this study, we obtained a highly effective expression of rabies glycoprotein mRNA molecule by the optimized mRNA preparation procedure and encapsulated with lipid nanoparticles (LNP), termed mRNA-LNP vaccine. A single dose of the mRNA-LNP was highly immunogenic and induced a rapid protective antibody response in mice. Antibodies play a pivotal role in protecting against lethal RABV infections and eliminate the virus by blocking it from invading the CNS. One dose of the mRNA-LNP vaccine induced higher and more durable VNA titers in dogs and cats compared with the licensed inactivated vaccines, intriguingly, the antibody titers were higher in cats than in dogs. Furthermore, the immunogenicity of the freeze-dried vaccine was not significantly declined when compared with a freshly prepared vaccine, and it can be stored at -20℃ for 4 months. All the above results show that the mRNA-LNP vaccine is safe and effectively exhibited robust immune responses both for dogs and cats with a single-dose administration, which being promising to be a candidate vaccine against rabies.
狂犬病是一种由狂犬病病毒（RABV）引起的人畜共患病。RABV感染会对中枢神经系统造成严重破坏，导致致命后果，这促使全球致力于研发高效且安全的疫苗。目前，使用最广泛的疫苗是灭活疫苗，无论是暴露前预防还是暴露后免疫都需要多次注射剂量。这增加了许多不必要的麻烦和劳动力成本。mRNA疫苗是对抗新出现和再次出现的传染病的一个有前景的平台，因为它们可以诱导高水平的病毒中和抗体（VNA）。在本研究中，我们通过优化的mRNA制备程序获得了狂犬病糖蛋白mRNA分子的高效表达，并将其封装在脂质纳米颗粒（LNP）中，称为mRNA-LNP疫苗。单剂量的mRNA-LNP具有高度免疫原性，并在小鼠中诱导了快速的保护性抗体反应。抗体在预防致命的RABV感染中起关键作用，并通过阻止病毒侵入中枢神经系统来消除病毒。与许可的灭活疫苗相比，单剂量的mRNA-LNP疫苗在犬猫中诱导出更高且更持久的VNA滴度，有趣的是，猫中的抗体滴度高于犬。此外，与新鲜制备的疫苗相比，冻干疫苗的免疫原性没有显著下降，并且可以在-20℃下储存4个月。上述所有结果表明，mRNA-LNP疫苗安全有效，单剂量给药对犬猫均表现出强大的免疫反应，有望成为一种狂犬病候选疫苗。
