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.

Zezhong Liu;Jie Zhou;Wei Xu;Wei Deng;Yanqun Wang;Meiyu Wang;Qian Wang;Ming Hsieh;Jingming Dong;Xinling Wang;Weijin Huangei;Lixiao Xing;Miaoling He;Chunlin Tao;Youhua Xie;Yilong Zhang;Youchun Wang;Jincun Zhao;Zhenghong Yuan;Chuan Qin;Shibo Jiang;Lu Lu

Key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS),School of Basic Medical Sciences;Shanghai Institute of Infectious Disease and Blosecurity;Biosafety Level 3 Laboratory,Shanghai Medical College,Shanghai Frontiers Science Center of Pathogenic Microbes and Infection,Fudan University,Shanghai,China;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;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;Institute of Infectious Disease,Guangzhou Eighth People's Hospital of Guangzhou Medical University,Guangzhou,Guangdong,China;Guangzhou Laboratory,Bio-Island,Guangzhou,China;Graduate School of Peking Union Medical College,No.9 Dongdan Santiao,Dongcheng District,Beijing,China;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;Fulgent Pharma LLC.,4978 Santa Anita Avenue,Temple City,CA,USA

细胞研究（英文版）

[1]Zezhong Liu;Jie Zhou;Wei Xu;Wei Deng;Yanqun Wang;Meiyu Wang;Qian Wang;Ming Hsieh;Jingming Dong;Xinling Wang;Weijin Huangei;Lixiao Xing;Miaoling He;Chunlin Tao;Youhua Xie;Yilong Zhang;Youchun Wang;Jincun Zhao;Zhenghong Yuan;Chuan Qin;Shibo Jiang;Lu Lu-.A novel STING agonist-adjuvanted pan-sarbecovirus vaccine elicits potent and durable neutralizing antibody and T cell responses in mice,rabbits and NHPs)[J].细胞研究（英文版）,2022(03):269-287

adjuvanted,sarbecovirus,sarbecoviruses,CF501,SARSr,nAbs

novel,STING,agonist,pan,elicits,durable,neutralizing,antibody,responses,mice,rabbits,NHPs,emergence,variants,potentially,other,highly,pathogenic,future,highlights,need,vaccines,Here,discovered,new,found,that,RBD,Fc,elicited,significantly,stronger,than,Alum,cGAMP,Vaccination,rhesus,macaques,nonhuman,primates,exceptionally,against,nine,mutants,CoVs,immunized,hACE2,transgenic,were,almost,completely,protected,challenge,even,months,after,initial,immunization,single,dose,produced,titers,also,exhibited,humoral,cellular,immune,showed,remarkably,reduced,viral,load,upper,lower,airways,upon,days,post,final,Thus,further,developed,combat,current,outbreaks,diseases

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