Li Yulei, Wang Xi, Zeng Xi, Ren Wenbo, Liao Pu, Zhu Baoli
Savaid Medical School University of Chinese Academy of Sciences Beijing China.
The Key Laboratory of Molecular Pathology (Hepatobiliary Diseases) of Guangxi, Department of Pathology The Affiliated Hospital of Youjiang Medical University for Nationalities Baise China.
mLife. 2023 Sep 24;2(3):308-316. doi: 10.1002/mlf2.12085. eCollection 2023 Sep.
Current influenza vaccines need to be updated annually owing to constant antigenic drift in the globular head of the viral surface hemagglutinin (HA) glycoprotein. The immunogenic subdominant stem domain of HA is highly conserved and can be recognized by antibodies capable of binding multiple HA subtypes. Therefore, the HA stem antigen is a promising target for the design of universal influenza vaccines. On the basis of an established lipid nanoparticle-encapsulated mRNA vaccine platform, we designed and developed a novel universal influenza mRNA vaccine (mHAs) encoding the HA stem antigen of the influenza A (H1N1) virus. We tested the efficacy of the mHAs vaccine using a mouse model. The vaccine induced robust humoral and specific cellular immune responses against the stem region of HA. Importantly, two doses of the mHAs vaccine fully protected mice from lethal challenges of the heterologous H1N1 and heterosubtypic H5N8 influenza viruses. Vaccinated mice had less pathological lung damage and lower viral titers than control mice. These results suggest that an mRNA vaccine using the conserved stem region of HA may provide effective protection against seasonal and other possible influenza variants.
由于病毒表面血凝素（HA）糖蛋白球状头部的抗原不断发生漂移，目前的流感疫苗需要每年更新。HA具有免疫原性的亚显性茎域高度保守，能够被可结合多种HA亚型的抗体识别。因此，HA茎抗原是设计通用流感疫苗的一个有前景的靶点。基于已建立的脂质纳米颗粒包裹的mRNA疫苗平台，我们设计并开发了一种新型通用流感mRNA疫苗（mHAs），其编码甲型流感病毒（H1N1）的HA茎抗原。我们使用小鼠模型测试了mHAs疫苗的效力。该疫苗诱导了针对HA茎区域的强大体液免疫和特异性细胞免疫反应。重要的是，两剂mHAs疫苗完全保护小鼠免受异源H1N1和异亚型H5N8流感病毒的致死性攻击。与对照小鼠相比，接种疫苗的小鼠肺部病理损伤较轻，病毒滴度较低。这些结果表明，使用HA保守茎区域的mRNA疫苗可能为预防季节性流感和其他可能的流感变种提供有效保护。
