Rapid development of double-hit mRNA antibody cocktail against orthopoxviruses  

作　　者：Hang Chi Suo-Qun Zhao Ru-Yi Chen Xing-Xing Suo Rong-Rong Zhang Wen-Hui Yang Dong-Sheng Zhou Min Fang Bo Ying Yong-Qiang Deng Cheng-Feng Qin 

机构地区：[1]State Key Laboratory of Pathogen and Biosecurity,Beijing Institute of Microbiology and Epidemiology,AMMS,100071,Beijing,China [2]College of Life Sciences,Inner Mongolia Agricultural University,Hohhot,010018,Inner Mongolia,China [3]School of Life Sciences,Henan University,Kaifeng,475004,Henan,China [4]Suzhou Abogen Biosciences Co.,Ltd,Suzhou,215123,Jiangsu,China [5]Research Unit of Discovery and Tracing of Natural Focus Diseases,Chinese Academy of Medical Sciences,100071,Beijing,China

出　　处：《Signal Transduction and Targeted Therapy》2024年第4期1768-1776,共9页信号转导与靶向治疗（英文）

基　　金：supported by the National Natural Science Foundation of China (No.82241069,and 82350801)to C.F.Q.;the National Key Research and Development Project of China (2021YFC2302400)to C.F.Q.;the Key-Area Research and Development Program of Guangdong Province (2022B1111020002).C.F.Q.;supported by the National Science Fund for Distinguished Young Scholars (81925025);the Innovation Fund for Medical Sciences (2019-12M-5-049)from the Chinese Academy of Medical Sciences.

摘　　要：The Orthopoxvirus genus,especially variola virus(VARV),monkeypox virus(MPXV),remains a significant public health threat worldwide.The development of therapeutic antibodies against orthopoxviruses is largely hampered by the high cost of antibody engineering and manufacturing processes.mRNA-encoded antibodies have emerged as a powerful and universal platform for rapid antibody production.Herein,by using the established lipid nanoparticle(LNP)-encapsulated mRNA platform,we constructed four mRNA combinations that encode monoclonal antibodies with broad neutralization activities against orthopoxviruses.In vivo characterization demonstrated that a single intravenous injection of each LNP-encapsulated mRNA antibody in mice resulted in the rapid production of neutralizing antibodies.More importantly,mRNA antibody treatments showed significant protection from weight loss and mortality in the vaccinia virus(VACV)lethal challenge mouse model,and a unique mRNA antibody cocktail,Mix2a,exhibited superior in vivo protection by targeting both intracellular mature virus(IMV)-form and extracellular enveloped virus(EEV)-form viruses.In summary,our results demonstrate the proof-of-concept production of orthopoxvirus antibodies via the LNP-mRNA platform,highlighting the great potential of tailored mRNA antibody combinations as a universal strategy to combat orthopoxvirus as well as otheremerging viruses.

关 键 词：proof universal NEUTRAL 

分 类 号：R511.3[医药卫生—内科学]