hLife (Mar 2025)
Enabling the immune escaped etesevimab fully-armed against SARS-CoV-2 Omicron subvariants including KP.2
- 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
Affiliations
- Chao Su
- Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China; CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China; Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Medicine, Zhongda Hospital, Advanced Institute for Life and Health, Southeast University, Jiangsu, China
- Juanhua He
- CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China; Institute of Pediatrics, Shenzhen Children's Hospital, Guangdong, China
- Yufeng Xie
- CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China; Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China
- Yu Hu
- CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China; School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui, China
- Xin Li
- CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
- Shitong Qiao
- CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China
- Peipei Liu
- NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
- Min Huang
- CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
- Rong Zhang
- CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China; State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Guangxi, China
- Liang Wang
- 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
- Zhen Chang
- Department of Pathogen Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
- Wenqiao Sun
- CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China; Institute of Physical Science and Information, Anhui University, Anhui, China
- Ke Xu
- NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
- Jing Zhang
- NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
- Longxing Cao
- School of Life Sciences, Westlake University, Zhejiang, China
- Pengcheng Han
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Medicine, Zhongda Hospital, Advanced Institute for Life and Health, Southeast University, Jiangsu, China
- Xin Zhao
- CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
- Jianxun Qi
- CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
- Qihui Wang
- CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
- Mengsu Yang
- Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China; Correspondence:
- George Fu Gao
- Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China; CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China; Correspondence:
- Journal volume & issue
-
Vol. 3,
no. 3
pp. 132 – 145
Abstract
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.
