iScience (Jun 2023)
Potent neutralizing broad-spectrum antibody against SARS-CoV-2 generated from dual-antigen-specific B cells from convalescents
- Masaru Takeshita,
- Hidehiro Fukuyama,
- Katsuhiko Kamada,
- Takehisa Matsumoto,
- Chieko Makino-Okamura,
- Qingshun Lin,
- Machie Sakuma,
- Eiki Kawahara,
- Isato Yamazaki,
- Tomomi Uchikubo-Kamo,
- Yuri Tomabechi,
- Kazuharu Hanada,
- Tamao Hisano,
- Saya Moriyama,
- Yoshimasa Takahashi,
- Mutsumi Ito,
- Masaki Imai,
- Tadashi Maemura,
- Yuri Furusawa,
- Seiya Yamayoshi,
- Yoshihiro Kawaoka,
- Mikako Shirouzu,
- Makoto Ishii,
- Hideyuki Saya,
- Yasushi Kondo,
- Yuko Kaneko,
- Katsuya Suzuki,
- Koichi Fukunaga,
- Tsutomu Takeuchi
Affiliations
- Masaru Takeshita
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan; Corresponding author
- Hidehiro Fukuyama
- Near-InfraRed Photo-Immunotherapy Research Institute, Kansai Medical University, Hirakata, Osaka 573-1010, Japan; RIKEN Center for Integrative Medical Sciences, Infectious Diseases Research Unit, Kanagawa 230-0045, Japan; Cell Integrative Science Laboratory, Graduate School of Medical Life Science, Yokohama City University, Kanagawa 230-0045, Japan; INSERM EST, Strasbourg Cedex 2, 67037, France
- Katsuhiko Kamada
- RIKEN Center for Biosystems Dynamics Research, Kanagawa 230-0045, Japan
- Takehisa Matsumoto
- RIKEN Center for Biosystems Dynamics Research, Kanagawa 230-0045, Japan
- Chieko Makino-Okamura
- Near-InfraRed Photo-Immunotherapy Research Institute, Kansai Medical University, Hirakata, Osaka 573-1010, Japan; RIKEN Center for Integrative Medical Sciences, Infectious Diseases Research Unit, Kanagawa 230-0045, Japan
- Qingshun Lin
- RIKEN Center for Integrative Medical Sciences, Infectious Diseases Research Unit, Kanagawa 230-0045, Japan
- Machie Sakuma
- RIKEN Center for Integrative Medical Sciences, Infectious Diseases Research Unit, Kanagawa 230-0045, Japan
- Eiki Kawahara
- Near-InfraRed Photo-Immunotherapy Research Institute, Kansai Medical University, Hirakata, Osaka 573-1010, Japan; RIKEN Center for Integrative Medical Sciences, Infectious Diseases Research Unit, Kanagawa 230-0045, Japan; Cell Integrative Science Laboratory, Graduate School of Medical Life Science, Yokohama City University, Kanagawa 230-0045, Japan
- Isato Yamazaki
- Near-InfraRed Photo-Immunotherapy Research Institute, Kansai Medical University, Hirakata, Osaka 573-1010, Japan; RIKEN Center for Integrative Medical Sciences, Infectious Diseases Research Unit, Kanagawa 230-0045, Japan; Cell Integrative Science Laboratory, Graduate School of Medical Life Science, Yokohama City University, Kanagawa 230-0045, Japan
- Tomomi Uchikubo-Kamo
- RIKEN Center for Biosystems Dynamics Research, Kanagawa 230-0045, Japan
- Yuri Tomabechi
- RIKEN Center for Biosystems Dynamics Research, Kanagawa 230-0045, Japan
- Kazuharu Hanada
- RIKEN Center for Biosystems Dynamics Research, Kanagawa 230-0045, Japan
- Tamao Hisano
- RIKEN Center for Biosystems Dynamics Research, Kanagawa 230-0045, Japan
- Saya Moriyama
- Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
- Yoshimasa Takahashi
- Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
- Mutsumi Ito
- Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
- Masaki Imai
- Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan; Center for Global Viral Diseases, National Center for Global Health and Medicine, Tokyo 162-8655, Japan
- Tadashi Maemura
- Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA
- Yuri Furusawa
- Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan; Center for Global Viral Diseases, National Center for Global Health and Medicine, Tokyo 162-8655, Japan
- Seiya Yamayoshi
- Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan; Center for Global Viral Diseases, National Center for Global Health and Medicine, Tokyo 162-8655, Japan
- Yoshihiro Kawaoka
- Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan; Center for Global Viral Diseases, National Center for Global Health and Medicine, Tokyo 162-8655, Japan; Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA
- Mikako Shirouzu
- RIKEN Center for Biosystems Dynamics Research, Kanagawa 230-0045, Japan
- Makoto Ishii
- Division of Pulmonary Medicine, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
- Hideyuki Saya
- Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine; Tokyo 162-8640, Japan
- Yasushi Kondo
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
- Yuko Kaneko
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
- Katsuya Suzuki
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
- Koichi Fukunaga
- Division of Pulmonary Medicine, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
- Tsutomu Takeuchi
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan; Saitama Medical University, Saitama 350-0495, Japan
- Journal volume & issue
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Vol. 26,
no. 6
p. 106955
Abstract
Summary: Several antibody therapeutics have been developed against SARS-CoV-2; however, they have attenuated neutralizing ability against variants. In this study, we generated multiple broadly neutralizing antibodies from B cells of convalescents, by using two types of receptor-binding domains, Wuhan strain and the Gamma variant as bait. From 172 antibodies generated, six antibodies neutralized all strains prior to the Omicron variant, and the five antibodies were able to neutralize some of the Omicron sub-strains. Structural analysis showed that these antibodies have a variety of characteristic binding modes, such as ACE2 mimicry. We subjected a representative antibody to the hamster infection model after introduction of the N297A modification, and observed a dose-dependent reduction of the lung viral titer, even at a dose of 2 mg/kg. These results demonstrated that our antibodies have certain antiviral activity as therapeutics, and highlighted the importance of initial cell-screening strategy for the efficient development of therapeutic antibodies.
