Multiple new variants of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)have constantly emerged,as the delta and omicron variants,which have developed resistance to currently gained neutralizing antibodies.This highlights a critical need to discover new therapeutic agents to overcome the variants mutations.Despite the availability of vaccines against coronavirus disease 2019(COVID-19),the use of broadly neutralizing antibodies has been considered as an alternative way for the prevention or treatment of SARS-CoV-2 variants infection.Here,we show that the nasal delivery of two previously characterized broadly neutralizing antibodies(F61 and H1 21)protected K18-hACE2 mice against lethal challenge with SARS-CoV-2 variants.The broadly protective efficacy of the F61 or F61/F121 cocktail antibodies was evaluated by lethal challenge with the wild strain(WIV04)and multiple variants,including beta(B.1.351),delta(B.1.617.2),and omicron(B.1.1.529)at 200 or 1000 TCID50,and the minimum antibody administration doses(5-1.25 mg/kg body weight)were also eval-uated with delta and omicron challenge.Fully prophylactic protections were found in all challenged groups with both F61 and F61/H121 combination at the administration dose of 20 mg/kg body weight,and corresponding mice lung viral RNA showed negative,with almost all alveolar septa and cavities remaining normal.Furthermore,low-dose antibody treatment induced significant prophylactic protection against lethal challenge with delta and omicron variants,whereas the F61/H121 combination showed excellent results against omicron infection.Our findings indicated the potential use of broadly neutralizing monoclonal antibodies as prophylactic and therapeutic agent for protection of current emerged SARS-CoV-2 variants infection.

Jia Lu;Qiangling Yin;Rongjuan Pei;Qiu Zhang;Yuanyuan Qu;Yongbing Pan;Lina Sun;Ding Gao;Cuiqin Liang;Jingwen Yang;Wei Wu;Jiandong Li;Zongqiang Cui;Zejun Wang;Xinguo Li;Dexin Li;Shiwen Wang;Kai Duan;Wuxiang Guan;Mifang Lian;Xiaoming Yang

National Engineering Technology Research Center for Combined Vaccines,Wuhan Institute of Biological Products Co.Ltd.,Wuhan,430070,China;State Key Laboratory for Molecular Virology and Genetic Engineering National Institute for Viral Disease Control and Prevention,Chinese Center for Disease Control and Prevention,Beijing,102206,China;Center for Emerging Infectious Diseases,Wuhan Institute of Virology,Chinese Academy of Sciences,Wuhan,430071,China;CDC-WIV Joint Research Center for Emerging Diseases and Biosafety,Wuhan,430071,China;Institution of Infectious Diseases,Shenzhen Bay Laboratory,Shenzhen,518107,China

中国病毒学

[1]Jia Lu;Qiangling Yin;Rongjuan Pei;Qiu Zhang;Yuanyuan Qu;Yongbing Pan;Lina Sun;Ding Gao;Cuiqin Liang;Jingwen Yang;Wei Wu;Jiandong Li;Zongqiang Cui;Zejun Wang;Xinguo Li;Dexin Li;Shiwen Wang;Kai Duan;Wuxiang Guan;Mifang Lian;Xiaoming Yang-.Nasal delivery of broadly neutralizing antibodies protects mice from lethal challenge with SARS-CoV-2 delta and omicron variants)[J].中国病毒学,2022(02):238-247

F61,F121,WIV04,H121,septa

Nasal,delivery,broadly,neutralizing,antibodies,protects,mice,from,lethal,SARS,CoV,delta,omicron,variants,Multiple,new,severe,acute,respiratory,syndrome,coronavirus,have,constantly,emerged,which,developed,resistance,currently,gained,This,highlights,critical,need,discover,therapeutic,agents,overcome,mutations,Despite,availability,vaccines,against,disease,use,has,been,considered,alternative,way,prevention,treatment,infection,Here,that,nasal,two,previously,characterized,protected,K18,hACE2,protective,efficacy,cocktail,was,evaluated,by,wild,strain,multiple,including,beta,TCID50,minimum,antibody,administration,doses,weight,were,also,Fully,prophylactic,protections,found,challenged,groups,both,combination,corresponding,lung,viral,showed,negative,almost,alveolar,cavities,remaining,normal,Furthermore,low,induced,significant,whereas,excellent,results,Our,findings,indicated,potential,monoclonal

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