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A novel STING agonist-adjuvanted pan-sarbecovirus vaccine elicits potent and durable neutralizing antibody and T cell responses in mice,rabbits and NHPs

查看全文 作　　者：Zezhong [1]Liu;Jie [1]Zhou;Wei [1]Xu;Wei [2]Deng;Yanqun [3,4,5]Wang;Meiyu [6,7]Wang;Qian [1]Wang;Ming [8]Hsieh;Jingming [8]Dong;Xinling [1]Wang;Weijin [6,7]Huang;Lixiao [1]Xing;Miaoling [8]He;Chunlin [8]Tao;Youhua [1]Xie;Yilong [8]Zhang;Youchun [6,7]Wang;Jincun [3,4,5]Zhao;Zhenghong [1]Yuan;Chuan [2]Qin;Shibo [1]Jiang;Lu [1]Lu 高影响力作者 机构地区：[1]Key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS),School of Basic Medical Sciences,Shanghai Institute of Infectious Disease and Biosecurity,Biosafety Level 3 Laboratory,Shanghai Medical College,Shanghai Frontiers Science Center of Pathogenic Microbes and Infection,Fudari University,Shanghai,China;[2]Key Laboratory of Human Disease Comparative Medicine,National Health Commission of the People's Republic of China,Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases,Institute of Laboratory Animal Science,Chinese Academy of Medical Sciences and Comparative Medicine Center,Peking Union Medical College,Beijing,China;[3]State Key Laboratory of Respiratory Disease,National Clinical Research Center for Respiratory Disease,Guangzhou Institute of Respiratory Health,the First Affiliated Hospital of Guangzhou Medical University,Guangzhou,Guangdong,China;[4]Institute of Infectious Disease,Guangzhou Eighth People's Hospital of Guangzhou Medical University,Guangzhou,Guangdong,China;[5]Guangzhou Laboratory,Bio-Island,Guangzhou,China;[6]Graduate School of Peking Union Medical College,No.9 Dongdan Santiao,Dongcheng District,Beijing,China;[7]Division of HIV/AIDS and Sex-transmitted Virus Vaccines,Institute for Biological Product Control,National Institutes for Food and Drug Control(NIFDC),No.31 Huatuo Street,Daxing District,Beijing,China;[8]Fulgent Pharma LLC.,4978 Santa Anita Avenue,Temple City,CA,USA高影响力机构 出　　处：《Cell Research》索引2022年第32卷第3期,共19页高影响力期刊 基　　金：We thank members of the Core Facility of Microbiology and Parasitology(SHMC)and the Biosafety Level 3 Laboratory at Shanghai Medical College of Fudan Unlversity,especially Dr.Di Qu,Dr.Xia Cail,Dr.Chengjian Gu,and Gaowei Hu for their technical assistance in this study;This work was supported by the National Natural Science Foundation of China(81822045 and 82041036 to L.L.,82041025 and 92169112 to SJ.);Program of Shanghai Academic/Technology Research Leader(20XD1420300 to L.L.);the National Key R&D Program of China(2021YFC0863300 to C.Q.);the China Postdoctoral Science Foundation(2021M700840 to Z.L.). 摘　　要：The emergence of SARS-CoV-2 variants and potentially other highly pathogenic sarbecoviruses in the future highlights the need for pan-sarbecovirus vaccines.Here,we discovered a new STING agonist,CF501,and found that CF501-adjuvanted RBD-FC vaccine(CF501/RBD-FC)elicited significantly stronger neutralizing antibody(nAb)and T cell responses than Alum-and cGAMP-adjuvanted RBD-FC in mice.Vaccination of rabbits and rhesus macaques(nonhuman primates,NHPs)with CF501/RBD-FC elicited exceptionally potent nAb responses against SARS-CoV-2 and its nine variants and 41 S-mutants,SARS-CoV and bat SARSr-CoVs.CF501/RBD-FC-immunized hACE2-transgenic mice were almost completely protected against SARS-CoV-2 challenge,even 6 months after the initial immunization.NHPs immunized with a single dose of CF501/RBD-FC produced high titers of nAbs.The immunized macaques also exhibited durable humoral and cellular immune responses and showed remarkably reduced viral load in the upper and lower airways upon SARS-CoV-2 challenge even at 108 days post the final immunization.Thus,CF501/RBD-Fc can be further developed as a novel pan-sarbecovirus vaccine to combat current and future outbreaks of sarbecovirus diseases. 关 键 词：vaccine ADJUVANT RABBITS
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