Chen Junyu, Wang Pui, Yuan Lunzhi, Zhang Liang, Zhang Limin, Zhao Hui, Chen Congjie, Wang Xijing, Han Jinle, Chen Yaode, Jia Jizong, Lu Zhen, Hong Junping, Lu Zicen, Wang Qian, Chen Rirong, Qi Ruoyao, Ma Jian, Zhou Min, Yu Huan, Zhuang Chunlan, Liu Xiaohui, Han Qiangyuan, Wang Guosong, Su Yingying, Yuan Quan, Cheng Tong, Wu Ting, Ye Xiangzhong, Zhang Tianying, Li Changgui, Zhang Jun, Zhu Huachen, Chen Yixin, Chen Honglin, Xia Ningshao
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, China.
State Key Laboratory of Emerging Infectious Diseases, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China.
Sci Bull (Beijing). 2022 Jul 15;67(13):1372-1387. doi: 10.1016/j.scib.2022.05.018. Epub 2022 May 26.
Remarkable progress has been made in developing intramuscular vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, they are limited with respect to eliciting local immunity in the respiratory tract, which is the primary infection site for SARS-CoV-2. To overcome the limitations of intramuscular vaccines, we constructed a nasal vaccine candidate based on an influenza vector by inserting a gene encoding the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2, named CA4-dNS1-nCoV-RBD (dNS1-RBD). A preclinical study showed that in hamsters challenged 1 d after single-dose vaccination or 9 months after booster vaccination, dNS1-RBD largely mitigated lung pathology, with no loss of body weight. Moreover, such cellular immunity is relatively unimpaired for the most concerning SARS-CoV-2 variants, especially for the latest Omicron variant. In addition, this vaccine also provides cross-protection against H1N1 and H5N1 influenza viruses. The protective immune mechanism of dNS1-RBD could be attributed to the innate immune response in the nasal epithelium, local RBD-specific T cell response in the lung, and RBD-specific IgA and IgG response. Thus, this study demonstrates that the intranasally delivered dNS1-RBD vaccine candidate may offer an important addition to the fight against the ongoing coronavirus disease 2019 pandemic and influenza infection, compensating limitations of current intramuscular vaccines.
在开发针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的肌肉注射疫苗方面已取得显著进展；然而，它们在引发呼吸道局部免疫方面存在局限性，而呼吸道是SARS-CoV-2的主要感染部位。为了克服肌肉注射疫苗的局限性，我们构建了一种基于流感载体的鼻用候选疫苗，通过插入编码SARS-CoV-2刺突蛋白受体结合域（RBD）的基因，命名为CA4-dNS1-nCoV-RBD（dNS1-RBD）。一项临床前研究表明，在单剂量疫苗接种后1天或加强疫苗接种后9个月进行攻击的仓鼠中，dNS1-RBD在很大程度上减轻了肺部病理变化，且体重未减轻。此外，对于最令人担忧的SARS-CoV-2变体，尤其是最新的奥密克戎变体，这种细胞免疫相对未受损害。此外，这种疫苗还对H1N1和H5N1流感病毒提供交叉保护。dNS1-RBD的保护性免疫机制可归因于鼻上皮中的先天免疫反应、肺部局部RBD特异性T细胞反应以及RBD特异性IgA和IgG反应。因此，这项研究表明，鼻内递送的dNS1-RBD候选疫苗可能为抗击当前的2019冠状病毒病大流行和流感感染提供重要补充，弥补当前肌肉注射疫苗的局限性。
