Laboratory of Veterinary Public Health, College of Veterinary Medicine, Chungnam National University, Daejeon, 34134, Republic of Korea.
Research Institute of Veterinary Research, Chungnam National University, Daejeon, 34134, Republic of Korea.
Virol J. 2022 Jun 27;19(1):112. doi: 10.1186/s12985-022-01844-9.
Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory disease in humans, with a case fatality rate of approximately 35%, thus posing a considerable threat to public health. The lack of approved vaccines or antivirals currently constitutes a barrier in controlling disease outbreaks and spread.
In this study, using a mammalian expression system, which is advantageous for maintaining correct protein glycosylation patterns, we constructed chimeric MERS-CoV virus-like particles (VLPs) and determined their immunogenicity and protective efficacy in mice.
Western blot and cryo-electron microscopy analyses demonstrated that MERS-CoV VLPs were efficiently produced in cells co-transfected with MERS-CoV spike (S), envelope, membrane and murine hepatitis virus nucleocapsid genes. We examined their ability as a vaccine in a human dipeptidyl peptidase 4 knock-in C57BL/6 congenic mouse model. Mice immunized with MERS VLPs produced S-specific antibodies with virus neutralization activity. Furthermore, MERS-CoV VLP immunization provided complete protection against a lethal challenge with mouse-adapted MERS-CoV and improved virus clearance in the lung.
Overall, these data demonstrate that MERS-CoV VLPs have excellent immunogenicity and represent a promising vaccine candidate.
中东呼吸综合征冠状病毒（MERS-CoV）可导致人类罹患严重呼吸道疾病，病死率约为 35%，因此对公共卫生构成重大威胁。目前，尚无获得批准的疫苗或抗病毒药物，这对控制疾病暴发和传播构成了障碍。
本研究采用哺乳动物表达系统，该系统有利于维持正确的蛋白糖基化模式，构建了嵌合 MERS-CoV 病毒样颗粒（VLPs），并在小鼠中评估了其免疫原性和保护效力。
Western blot 和 cryo-electron microscopy 分析表明，在共转染 MERS-CoV 刺突（S）、包膜、膜和鼠肝炎病毒核衣壳基因的细胞中，MERS-CoV VLPs 可高效表达。我们在人二肽基肽酶 4 敲入 C57BL/6 同源小鼠模型中检验了其作为疫苗的能力。用 MERS VLPs 免疫的小鼠可产生具有病毒中和活性的 S 特异性抗体。此外，MERS-CoV VLP 免疫可完全防止致死性的小鼠适应型 MERS-CoV 攻毒，并改善肺部病毒清除。
总体而言，这些数据表明 MERS-CoV VLPs 具有良好的免疫原性，是一种很有前途的候选疫苗。
