Frontiers in Cellular and Infection Microbiology (Aug 2023)
Broad-spectrum humanized monoclonal neutralizing antibody against SARS-CoV-2 variants, including the Omicron variant
- Kun Wen,
- Jian-Piao Cai,
- Xiaodi Fan,
- Xiaodi Fan,
- Xiaojuan Zhang,
- Cuiting Luo,
- Kai-Ming Tang,
- Huiping Shuai,
- Lin-Lei Chen,
- Ricky Ruiqi Zhang,
- Jianwen Situ,
- Hoi-Wah Tsoi,
- Kun Wang,
- Jasper Fuk-Woo Chan,
- Jasper Fuk-Woo Chan,
- Jasper Fuk-Woo Chan,
- Jasper Fuk-Woo Chan,
- Shuofeng Yuan,
- Shuofeng Yuan,
- Shuofeng Yuan,
- Shuofeng Yuan,
- Kwok-Yung Yuen,
- Kwok-Yung Yuen,
- Kwok-Yung Yuen,
- Kwok-Yung Yuen,
- Hongwei Zhou,
- Kelvin Kai-Wang To,
- Kelvin Kai-Wang To,
- Kelvin Kai-Wang To,
- Kelvin Kai-Wang To
Affiliations
- Kun Wen
- Microbiome Medicine Center, Division of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China
- Jian-Piao Cai
- State Key Laboratory for Emerging Infectious Diseases, Carol Yu Center for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, Pokfulam, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
- Xiaodi Fan
- Microbiome Medicine Center, Division of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China
- Xiaodi Fan
- Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, China
- Xiaojuan Zhang
- State Key Laboratory for Emerging Infectious Diseases, Carol Yu Center for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, Pokfulam, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
- Cuiting Luo
- State Key Laboratory for Emerging Infectious Diseases, Carol Yu Center for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, Pokfulam, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
- Kai-Ming Tang
- State Key Laboratory for Emerging Infectious Diseases, Carol Yu Center for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, Pokfulam, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
- Huiping Shuai
- State Key Laboratory for Emerging Infectious Diseases, Carol Yu Center for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, Pokfulam, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
- Lin-Lei Chen
- State Key Laboratory for Emerging Infectious Diseases, Carol Yu Center for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, Pokfulam, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
- Ricky Ruiqi Zhang
- State Key Laboratory for Emerging Infectious Diseases, Carol Yu Center for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, Pokfulam, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
- Jianwen Situ
- State Key Laboratory for Emerging Infectious Diseases, Carol Yu Center for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, Pokfulam, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
- Hoi-Wah Tsoi
- State Key Laboratory for Emerging Infectious Diseases, Carol Yu Center for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, Pokfulam, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
- Kun Wang
- State Key Laboratory for Emerging Infectious Diseases, Carol Yu Center for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, Pokfulam, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
- Jasper Fuk-Woo Chan
- State Key Laboratory for Emerging Infectious Diseases, Carol Yu Center for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, Pokfulam, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
- Jasper Fuk-Woo Chan
- Department of Microbiology, Queen Mary Hospital, Pokfulam, Hong Kong SAR, China
- Jasper Fuk-Woo Chan
- Department of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
- Jasper Fuk-Woo Chan
- Center for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong, Hong Kong SAR, China
- Shuofeng Yuan
- State Key Laboratory for Emerging Infectious Diseases, Carol Yu Center for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, Pokfulam, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
- Shuofeng Yuan
- Department of Microbiology, Queen Mary Hospital, Pokfulam, Hong Kong SAR, China
- Shuofeng Yuan
- Department of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
- Shuofeng Yuan
- Center for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong, Hong Kong SAR, China
- Kwok-Yung Yuen
- State Key Laboratory for Emerging Infectious Diseases, Carol Yu Center for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, Pokfulam, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
- Kwok-Yung Yuen
- Department of Microbiology, Queen Mary Hospital, Pokfulam, Hong Kong SAR, China
- Kwok-Yung Yuen
- Department of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
- Kwok-Yung Yuen
- Center for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong, Hong Kong SAR, China
- Hongwei Zhou
- Microbiome Medicine Center, Division of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China
- Kelvin Kai-Wang To
- State Key Laboratory for Emerging Infectious Diseases, Carol Yu Center for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, Pokfulam, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
- Kelvin Kai-Wang To
- Department of Microbiology, Queen Mary Hospital, Pokfulam, Hong Kong SAR, China
- Kelvin Kai-Wang To
- Department of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
- Kelvin Kai-Wang To
- Center for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong, Hong Kong SAR, China
- DOI
- https://doi.org/10.3389/fcimb.2023.1213806
- Journal volume & issue
-
Vol. 13
Abstract
IntroductionTherapeutic monoclonal antibodies (mAbs) against the SARS-CoV-2 spike protein have been shown to improve the outcome of severe COVID-19 patients in clinical trials. However, novel variants with spike protein mutations can render many currently available mAbs ineffective.MethodsWe produced mAbs by using hybridoma cells that generated from mice immunized with spike protein trimer and receptor binding domain (RBD). The panel of mAbs were screened for binding and neutralizing activity against different SARS-CoV-2 variants. The in vivo effectiveness of WKS13 was evaluated in a hamster model.ResultsOut of 960 clones, we identified 18 mAbs that could bind spike protein. Ten of the mAbs could attach to RBD, among which five had neutralizing activity against the ancestral strain and could block the binding between the spike protein and human ACE2. One of these mAbs, WKS13, had broad neutralizing activity against all Variants of Concern (VOCs), including the Omicron variant. Both murine or humanized versions of WKS13 could reduce the lung viral load in hamsters infected with the Delta variant.ConclusionsOur data showed that broad-spectrum high potency mAbs can be produced from immunized mice, which can be used in humans after humanization of the Fc region. Our method represents a versatile and rapid strategy for generating therapeutic mAbs for upcoming novel variants.
Keywords
