小鼠中严重发热伴血小板减少综合征mRNA候选疫苗的免疫原性和保护效果评估
The immunogenicity and protection efficacy evaluation of mRNA vaccine candidate for severe fever with thrombocytopenia syndrome in mice.
作者信息
Jeong Da-Eun, Yoon Jack, Kim Baek, Kang Jun-Gu
机构信息
Korea Zoonosis Research Institute, Jeonbuk National University, Iksan, Republic of Korea.
Vernagen LLC, Tucker, Georgia, United States of America.
出版信息
PLoS Negl Trop Dis. 2025 Apr 30;19(4):e0012999. doi: 10.1371/journal.pntd.0012999. eCollection 2025 Apr.
Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne viral pathogen that causes Severe fever with thrombocytopenia syndrome (SFTS) in humans with a high fatality rate. Currently, there are no approved antivirals or vaccines against SFTSV. The envelope protein of SFTSV, which consists of two domains, Gn and Gc, has been investigated as a target antigen for the development of SFTSV vaccines. Here, we used an mRNA platform to develop an effective and safe SFTSV vaccine. Our mRNA vaccine candidate harbored an equal number of mRNAs individually encoding the full-length SFTSV Gn or Gc domain. These mRNAs were produced using a 5' cap, SmartCap, by in vitro transcription and then packaged with an ionizable lipid nanoparticle platform, called STLNP. Robust expression of these Gn and Gc antigens was observed when human 293 T cells were transfected with the SFTSV mRNA formulation. When mice were immunized with our SFTSV vaccine candidate, the collected serum displayed strong immunogenicity and in vitro neutralization activity against SFTSV. Thus, the immunized mice showed complete protection with a lethal dose of SFTSV, without any pathological traces of SFTSV infection-mediated tissue damage. Thus, our mRNA vaccine platform is a promising SFTS vaccine candidate for clinical development.
严重发热伴血小板减少综合征病毒(SFTSV)是一种蜱传病毒病原体,可导致人类患上严重发热伴血小板减少综合征(SFTS),病死率很高。目前,尚无获批的针对SFTSV的抗病毒药物或疫苗。SFTSV的包膜蛋白由Gn和Gc两个结构域组成,已被研究作为开发SFTSV疫苗的靶抗原。在此,我们利用mRNA平台开发了一种有效且安全的SFTSV疫苗。我们的mRNA候选疫苗包含等量的分别编码全长SFTSV Gn或Gc结构域的mRNA。这些mRNA通过体外转录使用5'帽结构SmartCap产生,然后与一种名为STLNP的可电离脂质纳米颗粒平台进行包装。当用SFTSV mRNA制剂转染人293 T细胞时,观察到这些Gn和Gc抗原的强劲表达。当用我们的SFTSV候选疫苗免疫小鼠时,所收集的血清对SFTSV显示出强大的免疫原性和体外中和活性。因此,免疫的小鼠在接受致死剂量的SFTSV攻击后表现出完全的保护作用,没有任何SFTSV感染介导的组织损伤的病理痕迹。因此,我们的mRNA疫苗平台是一种有前景的用于临床开发的SFTS疫苗候选物。