Monoclonal antibodies represent important weapons in our arsenal to against the COVID-19 pandemic.However,this potential is severely limited by the time-consuming process of developing effective antibodies and the relative high cost of manufacturing.Herein,we present a rapid and cost-effective lipid nanoparticle(LNP)encapsulated-mRNA platform for in vivo delivery of SARS-CoV-2 neutralization antibodies.Two mRNAs encoding the light and heavy chains of a potent SARS-CoV-2 neutralizing antibody HB27,which is currently being evaluated in clinical trials,were encapsulated into clinical grade LNP formulations(named as mRNA-HB27-LNP).In vivo characterization demonstrated that intravenous administration of mRNA-HB27-LNP in mice resulted in a longer circulating half-life compared with the original HB27 antibody in protein format.More importantly,a single prophylactic administration of mRNA-HB27-LNP provided protection against SARS-CoV-2 challenge in mice at 1,7 and even 63 days post administration.In a close contact transmission model,prophylactic administration of mRNA-HB27-LNP prevented SARS-CoV-2 infection between hamsters in a dose-dependent manner.Overall,our results demonstrate a superior long-term protection against SARS-CoV-2 conferred by a single administration of this unique mRNA antibody,highlighting the potential of this universal platform for antibody-based disease prevention and therapy against COVID-19 as well as a variety of other infectious diseases.

Yong-Qiang Deng;Na-Na Zhang;Yi-Fei Zhang;Xia Zhong;Sue Xu;Hong-Ying Qiu;Tie-Cheng Wang;Hui Zhao;Chao Zhou;Shu-Long Zu;Qi Chen;Tian-Shu Cao;Qing Ye;Hang Chi;Xiang-Hui Duan;Dan-Dan Lin;Xiao-Jing Zhang;Liang-Zhi Xie;Yu-Wei Gao;Bo Ying;Cheng-Feng Qin

State Key Laboratory of Pathogen and Biosecurity,Beijing Institute of Microbiology and Epidemiology,AMMS,Beijing,China;School of Medicine,Tsinghua University,Beijing,China;Kunming University of Science and Technology,Kunming,Yunnan,China;Suzhou Abogen Biosciences Co.,Ltd,Suzhou,Jiangsu,China;Key laboratory of Jilin Province for Zoonosis Prevention and Control,Changchun,Jilin,China;Beijing Protein and Antibody R&D Engineering Center,Sinocelltech Ltd,Beijing,China

细胞研究（英文版）

[1]Yong-Qiang Deng;Na-Na Zhang;Yi-Fei Zhang;Xia Zhong;Sue Xu;Hong-Ying Qiu;Tie-Cheng Wang;Hui Zhao;Chao Zhou;Shu-Long Zu;Qi Chen;Tian-Shu Cao;Qing Ye;Hang Chi;Xiang-Hui Duan;Dan-Dan Lin;Xiao-Jing Zhang;Liang-Zhi Xie;Yu-Wei Gao;Bo Ying;Cheng-Feng Qin-.Lipid nanoparticle-encapsulated mRNA antibody provides long-term protection against SARS-CoV-2 in mice and hamsters)[J].细胞研究（英文版）,2022(04):375-382

HB27

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