A triple-RBD-based mucosal vaccine provides broad protectionagainst SARS-CoV-2 variants of concern  

作　　者：Jingyi Yang Mei-Qin Liu Lin Liu Xian Li Mengxin Xu Haofeng Lin Shuning Liu Yunqi Hu Bei Li Bowen Liu Min Li Ying Sun Yao-Qing Chen Zheng-Li Shi Huimin Yan 

机构地区：[1]Vaccine and Immunology Research Center,Translational Medical Research Institute,Shanghai Public Health Clinical Center,Fudan University,201508 Shanghai,China [2]Wuhan Institute of Virology,Chinese Academy of Sciences,430071 Wuhan,China [3]University of Chinese Academy of Sciences,100049 Beijing,China [4]School of Public Health(Shenzhen),Shenzhen Campus of Sun Yat-sen University,Shenzhen 518107 Guangdong,China [5]Aerosol Bio-Tech(Suzhou)Co.,LTD,Suzhou 215123 Jiangsu,China [6]Key Laboratory of Tropical Disease Control(Sun Yat-sen University),Ministry of Education,Guangzhou,China

出　　处：《Cellular & Molecular Immunology》2022年第11期1279-1289,共11页中国免疫学杂志（英文版）

基　　金：This work was supported in whole or in part by the National Key R&D Program of China(grant number:2021YFC2302602 to JY);the strategic priority research program(grant number XDB29010101);key project(2020YJFK-Z-0149)of the Chinese Academy of Sciences(to Z-LS);This study was also supported by the National Natural Science Foundation of China(31970878 to JY,92169104 and 31970881 to Y-QC),Shenzhen Science and Technology Program (Grant number: RCJC20210706092009004 and JCYJ20190807154603596 to Y-QC).

摘　　要：The rapid mutation and spread of SARS-CoV-2 variants urge the development of effective mucosal vaccines to provide broadspectrum protection against the initial infection and thereby curb the transmission potential.Here,we designed a chimeric tripleRBD immunogen,3Ro-NC,harboring one Delta RBD and two Omicron RBDs within a novel protein scaffold.3Ro-NC elicits potent and broad RBD-specific neutralizing immunity against SARS-CoV-2 variants of concern.Notably,intranasal immunization with 3RoNC plus the mucosal adjuvant KFD(3Ro-NC+KFDi.n)elicits coordinated mucosal IgA and higher neutralizing antibody specificity(closer antigenic distance)against the Omicron variant.In Omicron-challenged human ACE2 transgenic mice,3Ro-NC+KFDi.n immunization significantly reduces the tissue pathology in the lung and lowers the viral RNA copy numbers in both the lung(85.7-fold)and the nasal turbinate(13.6-fold).Nasal virologic control is highly correlated with RBD-specific secretory IgA antibodies.Our data show that 3Ro-NC plus KFD is a promising mucosal vaccine candidate for protection against SARS-CoV-2 Omicron infection,pathology and transmission potential.

关 键 词：SARS-CoV-2 Mucosal vaccine Intranasal immunization Triple-RBD Flagellin adjuvant Variant of concern 

分 类 号：R186[医药卫生—流行病学]