Intranasal delivery of a subunit protein vaccine provides protective immunity against JN.1 and XBB-lineage variants.
作者信息
Lei Hong, Hong Weiqi, Yang Jingyun, He Cai, Zhou Yanan, Zhang Yu, Alu Aqu, Shi Jie, Liu Jian, Qin Furong, Ao Danyi, Huang Xiya, Chen Zimin, Yang Hao, Yang Yun, Yu Wenhai, Tang Cong, Wang Junbin, Li Bai, Huang Qing, Hu Hongbo, Cheng Wei, Dong Haohao, Lei Jian, Chen Lu, Zhou Xikun, Li Jiong, Yang Li, Wang Zhenling, Wang Wei, Shen Guobo, Yang Jinliang, Zhao Zhiwei, Song Xiangrong, Lu Guangwen, Sun Qiangming, Wang Youchun, Lu Shuaiyao, Wei Xiawei
机构信息
Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, PR China.
National Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
出版信息
Signal Transduct Target Ther. 2024 Nov 20;9(1):311. doi: 10.1038/s41392-024-02025-6.
The mucosal immune response plays a crucial role in the prevention of respiratory viruses. Given the risk of recurrent SARS-CoV-2 infections in the population, the rapid development of next-generation intranasal COVID-19 vaccines with high safety and efficacy is paramount. In the current study, we developed a protein-based intranasal vaccine comprising the XBB.1.5 receptor binding domain (RBD)-derived trimeric recombinant protein (RBD-HR) and an MF59-like oil-in-water adjuvant. Intranasal administration of RBD-HR vaccine elicited robust and sustained humoral immune responses in mice and rats, resulting in high levels of neutralizing antibodies against XBB-lineage subvariants, with protection lasting for at least six months. The intranasal RBD-HR vaccine generated potent mucosal immune responses, characterized by the inductions of tissue-resident T (T) cells, local cellular immunity, germinal center, and memory B cell responses in the respiratory tract. The combination of intramuscular and intranasal delivery of the RBD-HR vaccine demonstrated exceptional systemic and mucosal protective immunity. Furthermore, intranasal delivery of RBD-HR vaccine as a heterologous booster shot showed more effective boosting effects after mRNA administration compared to homologous vaccination, as evidenced by the induction of superior systemic and extra mucosal immune response. Importantly, the intranasal RBD-HR vaccine conferred efficient protection against the challenge with authentic EG.5.1 viruses in vivo. These findings identify the intranasal RBD-HR vaccine as a potential mucosal vaccine candidate for the prevention of SARS-CoV-2 infection.