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

查看全文 作  者:Jingyi [1]Yang;Mei-Qin [2,3]Liu;Lin [4]Liu;Xian [1,2,3]Li;Mengxin [4]Xu;Haofeng [2,3]Lin;Shuning [4]Liu;Yunqi [4]Hu;Bei [2]Li;Bowen [2,3]Liu;Min [1]Li;Ying [5]Sun;Yao-Qing [4,6]Chen;Zheng-Li [2]Shi;Huimin [1]Yan 高影响力作者 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高影响力机构 出  处:《Cellular & Molecular Immunology》索引2022年第19卷第11期,共11页高影响力期刊 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
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