iScience (Dec 2022)
Potent SARS-CoV-2 neutralizing antibodies with therapeutic effects in two animal models
- Masaru Takeshita,
- Hidehiro Fukuyama,
- Katsuhiko Kamada,
- Takehisa Matsumoto,
- Chieko Makino-Okamura,
- Tomomi Uchikubo-Kamo,
- Yuri Tomabechi,
- Kazuharu Hanada,
- Saya Moriyama,
- Yoshimasa Takahashi,
- Hirohito Ishigaki,
- Misako Nakayama,
- Cong Thanh Nguyen,
- Yoshinori Kitagawa,
- Yasushi Itoh,
- Masaki Imai,
- Tadashi Maemura,
- Yuri Furusawa,
- Hiroshi Ueki,
- Kiyoko Iwatsuki-Horimoto,
- Mutsumi Ito,
- 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
- RIKEN Center for Integrative Medical Sciences, Infectious Diseases Research unit, Kanagawa 230-0045, Japan; RIKEN Center for Integrative Medical Sciences, Laboratory for Lymphocyte Differentiation, Kanagawa 230-0045, Japan; Cell Integrative Science Laboratory, Graduate School of Medical Life Science, Yokohama City University, Kanagawa 230-0045, Japan; INSERM EST, 67037 Strasbourg Cedex 2, France; Near-InfraRed Photo-Immunotherapy Research Institute, Kansai Medical University, Hirakata, Osaka, 573-1010, Japan
- Katsuhiko Kamada
- RIKEN Center for Biosystems Dynamics Research, Kanagawa 230-0045, Japan; Laboratory for Glycometabolic Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Saitama 351-0198, Japan
- Takehisa Matsumoto
- RIKEN Center for Biosystems Dynamics Research, Kanagawa 230-0045, Japan
- Chieko Makino-Okamura
- RIKEN Center for Integrative Medical Sciences, Laboratory for Lymphocyte Differentiation, 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
- 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
- Hirohito Ishigaki
- Department of Pathology, Shiga University of Medical Science, Shiga 520-2192, Japan
- Misako Nakayama
- Department of Pathology, Shiga University of Medical Science, Shiga 520-2192, Japan
- Cong Thanh Nguyen
- Department of Pathology, Shiga University of Medical Science, Shiga 520-2192, Japan
- Yoshinori Kitagawa
- Division of Microbiology and Infectious Diseases, Department of Pathology, Shiga University of Medical Science, Shiga 520-2192, Japan
- Yasushi Itoh
- Department of Pathology, Shiga University of Medical Science, Shiga 520-2192, 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
- Hiroshi Ueki
- 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
- Kiyoko Iwatsuki-Horimoto
- Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
- Mutsumi Ito
- Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, 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
- Journal volume & issue
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Vol. 25,
no. 12
p. 105596
Abstract
Summary: The use of therapeutic neutralizing antibodies against SARS-CoV-2 infection has been highly effective. However, there remain few practical antibodies against viruses that are acquiring mutations. In this study, we created 494 monoclonal antibodies from patients with COVID-19-convalescent, and identified antibodies that exhibited the comparable neutralizing ability to clinically used antibodies in the neutralization assay using pseudovirus and authentic virus including variants of concerns. These antibodies have different profiles against various mutations, which were confirmed by cell-based assay and cryo-electron microscopy. To prevent antibody-dependent enhancement, N297A modification was introduced. Our antibodies showed a reduction of lung viral RNAs by therapeutic administration in a hamster model. In addition, an antibody cocktail consisting of three antibodies was also administered therapeutically to a macaque model, which resulted in reduced viral titers of swabs and lungs and reduced lung tissue damage scores. These results showed that our antibodies have sufficient antiviral activity as therapeutic candidates.
