Nasal vaccination of triple-RBD scaffold protein with flagellin elicits long-term protection against SARS-CoV-2 variants including JN.1  

作　　者：Xian Li Mengxin Xu Jingyi Yang Li Zhou Lin Liu Min Li Shasha Wang Mei-Qin Liu Zhixiang Huang Zhen Zhang Shuning Liu Yunqi Hu Haofeng Lin Bowen Liu Ying Sun Qingguo Wu Zheng-Li Shi Ke Lan Yu Chen Huimin Yan Yao-Qing Chen 

机构地区：[1]Wuhan Institute of Virology,Chinese Academy of Sciences,Wuhan,China [2]Vaccine and Immunology Research Center,Translational Medical Research Institute,Shanghai Public Health Clinical Center,Fudan University,Shanghai,China [3]University of Chinese Academy of Sciences,Beijing,China [4]School of Public Health(Shenzhen),Shenzhen Campus of Sun Yat-sen University,Shenzhen,Guangdong,China [5]State Key Laboratory of Virology,Modern Virology Research Center,College of Life Sciences,Wuhan University,Wuhan,China [6]Aerosol Bio-Tech(Suzhou)Co.,LTD,Suzhou,Jiangsu,China [7]National Medical Products Administration Key Laboratory for Quality Monitoring and Evaluation of Vaccines and Biological Products,Sun Yat-sen University,Guanzhou,China

出　　处：《Signal Transduction and Targeted Therapy》2024年第5期2312-2323,共12页信号转导与靶向治疗（英文）

基　　金：National Key R&D program of China(Grant number:2022YFC2304204 to Y.-Q.C.,2021YFC2302602 to J.Y.);National Natural Science Foundation of China(grant number:82341041 to H.Y.and 92169104 to Y.-Q.C.);Shanghai Science and Technology Innovation Action Plan(Grant number:22Y11901000 to Q.W.);Shenzhen Science and Technology Program(Grant number:RCJC20210706092009004,JCYJ2020010914243811,KQTD20200820145822023 to Y.-Q.C.)supported this work in whole or in part.

摘　　要：Developing a mucosal vaccine against SARS-CoV-2 is critical for combatting the epidemic.Here,we investigated long-term immune responses and protection against SARS-CoV-2 for the intranasal vaccination of a triple receptor-binding domain(RBD)scaffold protein(3R-NC)adjuvanted with a flagellin protein(KFD)(3R-NC+KFDi.n).In mice,the vaccination elicited RBD-specific broad-neutralizing antibody responses in both serum and mucosal sites sustained at high level over a year.This long-lasting humoral immunity was correlated with the presence of long-lived RBD-specific IgG-and IgA-producing plasma cells,alongside the Th17 and Tfh17-biased T-cell responses driven by the KFD adjuvant.Based upon these preclinical findings,an open labeled clinical trial was conducted in individuals who had been primed with the inactivated SARS-CoV-2(IAV)vaccine.With a favorable safety profile,the 3R-NC+KFDi.n boost elicited enduring broad-neutralizing IgG in plasma and IgA in salivary secretions.To meet the challenge of frequently emerged variants,we further designed an updated triple-RBD scaffold protein with mutated RBD combinations,which can induce adaptable antibody responses to neutralize the newly emerging variants,including JN.1.Our findings highlight the potential of the KFD-adjuvanted triple-RBD scaffold protein is a promising prototype for the development of a mucosal vaccine against SARS-CoV-2 infection.

关 键 词：VACCINATION VACCINE SUSTAINED 

分 类 号：R392-33[医药卫生—免疫学]