Enabling the immune escaped etesevimab fully-armed against SARS-CoV-2 Omicron subvariants including KP.2  

作　　者：Chao Su Juanhua He Yufeng Xie Yu Hu Xin Li Shitong Qiao Peipei Liu Min Huang Rong Zhang Liang Wang Zhen Chang Wenqiao Sun Ke Xu Jing Zhang Longxing Cao Pengcheng Han Xin Zhao Jianxun Qi Qihui Wang Mengsu Yang George Fu Gao 

机构地区：[1]Department of Biomedical Sciences,City University of Hong Kong,Hong Kong,China [2]CAS Key Laboratory of Pathogen Microbiology and Immunology,Institute of Microbiology,Chinese Academy of Sciences,Beijing,China [3]Jiangsu Provincial Key Laboratory of Critical Care Medicine,School of Medicine,Zhongda Hospital,Advanced Institute for Life and Health,Southeast University,Jiangsu,China [4]Institute of Pediatrics,Shenzhen Children's Hospital,Guangdong,China [5]Department of Basic Medical Sciences,School of Medicine,Tsinghua University,Beijing,China [6]School of Life Sciences,Division of Life Sciences and Medicine,University of Science and Technology of China,Anhui,China [7]University of Chinese Academy of Sciences,Beijing,China [8]NHC Key Laboratory of Biosafety,National Institute for Viral Disease Control and Prevention,Chinese Center for Disease Control and Prevention,Beijing,China [9]State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources,Guangxi University,Guangxi,China [10]CAS Key Laboratory of Pathogen Microbiology and Immunology,Institute of Microbiology,Center for Influenza Research and Early-warning(CASCIRE),CAS-TWAS Center of Excellence for Emerging Infectious Diseases(CEEID),Chinese Academy of Sciences,Beijing,China [11]Department of Pathogen Microbiology,School of Basic Medical Sciences,Capital Medical University,Beijing,China [12]Institute of Physical Science and Information,Anhui University,Anhui,China [13]School of Life Sciences,Westlake University,Zhejiang,China

出　　处：《hLife》2025年第3期132-145,共14页微生物与宿主健康(英文)

基　　金：supported by the National Natural Science Foundation of China(82225021);the National Key R&D Program of China(2022YFC2303403,2021YFA1300803,2021YFA1301404).

摘　　要：Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is continuously evolving since 2019.Some monoclonal antibodies(mAbs)have been developed and widely used,such as etesevimab(CB6)developed by Eli-Lilly/Junshi.However,the mAb escaped from the variant of concern(VOC)ever since the emergence of Beta VOC,with a complete loss of efficacy against the Omicron subvariants.Here,we developed a broad-spectrum and affinity-mature antibody design(BAADesign)procedure to design CB6,enabling it to bind to the receptor-binding domains(RBDs)of multiple important Omicron subvariants,including the recent variant KP.2.Structural analysis confirmed the desired CB6-RBD interactions.Additionally,identical mutations in the complementarity determining regions(CDR)1 and CDR2 of the CB6 mutants also restored neutralizing potency for some RBD-1 group antibodies.Overall,the enhanced CB6 neutralizing capacity makes it a promising candidate against SARS-CoV-2 infection,and the BAADesign method has implications for the design of other antibodies.

关 键 词：etesevimab(CB6) severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) receptor-binding domain(RBD) broad-spectrum and affinity-mature antibody design(BAADesign) antibody 

分 类 号：R37[医药卫生—病原生物学]