Intranasal delivery of a subunit protein vaccine provides protective immunity against JN.1 and XBB-lineage variants  

作　　者：Hong Lei Weiqi Hong Jingyun Yang Cai He Yanan Zhou Yu Zhang Aqu Alu Jie Shi Jian Liu Furong qin Danyi Ao Xiya Huang Zimin Chen Hao Yang Yun Yang Wenhai Yu Cong Tang Junbin Wang Bai Li Qing Huang Hongbo Hu Wei Cheng Haohao Dong Jian Lei Lu Chen Xikun Zhou Jiong Li Li Yang Zhenling Wang Wei Wang Guobo Shen Jinliang Yang Zhiwei Zhao Xiangrong Song Guangwen Lu Qiangming Sun Youchun Wang Shuaiyao Lu Xiawei Wei 

机构地区：[1]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 [2]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　　处：《Signal Transduction and Targeted Therapy》2024年第12期5752-5764,共13页信号转导与靶向治疗(英文)

基　　金：supported by the National Science Foundation for Excellent Young Scholars(32122052,X.W.);National Natural Science Foundation Regional Innovation and Development(No.U19A2003,X.W.);National Natural Science Foundation of China(32300743,H.L.);the Project of the Science and Technology Department of Sichuan Province(NO.2024NSFSC1757,H.L.);National Natural Science Foundation of China Young Student Basic Research Program(323B2050,W.H.)。

摘　　要：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_(XBB.1.5)-HR)and an MF59-like oil-in-water adjuvant.Intranasal administration of RBD_(XBB.1.5)-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_(XBB.1.5)-HR vaccine generated potent mucosal immune responses,characterized by the inductions of tissue-resident T(TRM)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_(XBB.1.5)-HR vaccine demonstrated exceptional systemic and mucosal protective immunity.Furthermore,intranasal delivery of RBD_(XBB.1.5)-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_(XBB.1.5)-HR vaccine conferred efficient protection against the challenge with authentic EG.5.1 viruses in vivo.These findings identify the intranasal RBD_(XBB.1.5)-HR vaccine as a potential mucosal vaccine candidate for the prevention of SARS-CoV-2 infection.

关 键 词：NASAL IMMUNITY protective 

分 类 号：R392[医药卫生—免疫学]