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

doi:10.1016/j.isci.2022.105596

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-HorimotoMutsumi Ito, Seiya Yamayoshi, Yoshihiro Kawaoka, Mikako Shirouzu, Makoto Ishii, Hideyuki Saya, Yasushi Kondo, Yuko Kaneko, Katsuya Suzuki, Koichi Fukunaga, Tsutomu Takeuchi

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

Abstract

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.

Original language	English
Article number	105596
Journal	iScience
Volume	25
Issue number	12
DOIs	https://doi.org/10.1016/j.isci.2022.105596
Publication status	Published - 22-12-2022
Externally published	Yes

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Takeshita, M., Fukuyama, H., Kamada, K., Matsumoto, T., Makino-Okamura, C., Uchikubo-Kamo, T., Tomabechi, Y., Hanada, K., Moriyama, S., Takahashi, Y., Ishigaki, H., Nakayama, M., Nguyen, C. T., Kitagawa, Y., Itoh, Y., Imai, M., Maemura, T., Furusawa, Y., Ueki, H., ... Takeuchi, T. (2022). Potent SARS-CoV-2 neutralizing antibodies with therapeutic effects in two animal models. iScience, 25(12), Article 105596. https://doi.org/10.1016/j.isci.2022.105596

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title = "Potent SARS-CoV-2 neutralizing antibodies with therapeutic effects in two animal models",

abstract = "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.",

author = "Masaru Takeshita and Hidehiro Fukuyama and Katsuhiko Kamada and Takehisa Matsumoto and Chieko Makino-Okamura and Tomomi Uchikubo-Kamo and Yuri Tomabechi and Kazuharu Hanada and Saya Moriyama and Yoshimasa Takahashi and Hirohito Ishigaki and Misako Nakayama and Nguyen, {Cong Thanh} and Yoshinori Kitagawa and Yasushi Itoh and Masaki Imai and Tadashi Maemura and Yuri Furusawa and Hiroshi Ueki and Kiyoko Iwatsuki-Horimoto and Mutsumi Ito and Seiya Yamayoshi and Yoshihiro Kawaoka and Mikako Shirouzu and Makoto Ishii and Hideyuki Saya and Yasushi Kondo and Yuko Kaneko and Katsuya Suzuki and Koichi Fukunaga and Tsutomu Takeuchi",

note = "Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2022",

month = dec,

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doi = "10.1016/j.isci.2022.105596",

language = "English",

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Takeshita, M, Fukuyama, H, Kamada, K, Matsumoto, T, Makino-Okamura, C, Uchikubo-Kamo, T, Tomabechi, Y, Hanada, K, Moriyama, S, Takahashi, Y, Ishigaki, H, Nakayama, M, Nguyen, CT, Kitagawa, Y, Itoh, Y, Imai, M, Maemura, T, Furusawa, Y, Ueki, H, Iwatsuki-Horimoto, K, Ito, M, Yamayoshi, S, Kawaoka, Y, Shirouzu, M, Ishii, M, Saya, H, Kondo, Y, Kaneko, Y, Suzuki, K, Fukunaga, K & Takeuchi, T 2022, 'Potent SARS-CoV-2 neutralizing antibodies with therapeutic effects in two animal models', iScience, vol. 25, no. 12, 105596. https://doi.org/10.1016/j.isci.2022.105596

TY - JOUR

T1 - Potent SARS-CoV-2 neutralizing antibodies with therapeutic effects in two animal models

AU - Takeshita, Masaru

AU - Fukuyama, Hidehiro

AU - Kamada, Katsuhiko

AU - Matsumoto, Takehisa

AU - Makino-Okamura, Chieko

AU - Uchikubo-Kamo, Tomomi

AU - Tomabechi, Yuri

AU - Hanada, Kazuharu

AU - Moriyama, Saya

AU - Takahashi, Yoshimasa

AU - Ishigaki, Hirohito

AU - Nakayama, Misako

AU - Nguyen, Cong Thanh

AU - Kitagawa, Yoshinori

AU - Itoh, Yasushi

AU - Imai, Masaki

AU - Maemura, Tadashi

AU - Furusawa, Yuri

AU - Ueki, Hiroshi

AU - Iwatsuki-Horimoto, Kiyoko

AU - Ito, Mutsumi

AU - Yamayoshi, Seiya

AU - Kawaoka, Yoshihiro

AU - Shirouzu, Mikako

AU - Ishii, Makoto

AU - Saya, Hideyuki

AU - Kondo, Yasushi

AU - Kaneko, Yuko

AU - Suzuki, Katsuya

AU - Fukunaga, Koichi

AU - Takeuchi, Tsutomu

PY - 2022/12/22

Y1 - 2022/12/22

N2 - 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.

AB - 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.

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DO - 10.1016/j.isci.2022.105596

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AN - SCOPUS:85145599511

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VL - 25

JO - iScience

JF - iScience

IS - 12

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ER -

Potent SARS-CoV-2 neutralizing antibodies with therapeutic effects in two animal models

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