Japan Agency for Medical Research and Development (AMED)
JP21ym0126022
日本
引用
ジャーナル: iScience / 年: 2022 タイトル: Potent SARS-CoV-2 neutralizing antibodies with therapeutic effects in two animal models. 著者: Masaru Takeshita / Hidehiro Fukuyama / Katsuhiko Kamada / Takehisa Matsumoto / Chieko Makino-Okamura / Tomomi Uchikubo-Kamo / Yuri Tomabechi / Kazuharu Hanada / Saya Moriyama / Yoshimasa ...著者: 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 / 要旨: 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 ...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.
全体 : The SARS-CoV-2 spike protein bound with the Fab fragment of a hum...
全体
名称: The SARS-CoV-2 spike protein bound with the Fab fragment of a human neutralizing antibody Ab326
要素
複合体: The SARS-CoV-2 spike protein bound with the Fab fragment of a human neutralizing antibody Ab326
タンパク質・ペプチド: Ab326 heavy chain
タンパク質・ペプチド: Ab326 light chain
タンパク質・ペプチド: Spike glycoprotein
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超分子 #1: The SARS-CoV-2 spike protein bound with the Fab fragment of a hum...
超分子
名称: The SARS-CoV-2 spike protein bound with the Fab fragment of a human neutralizing antibody Ab326 タイプ: complex / キメラ: Yes / ID: 1 / 親要素: 0 / 含まれる分子: all
名称: Spike glycoprotein / タイプ: protein_or_peptide / ID: 3 詳細: From aa1209, additional tags are added at the C-terminal, with Foldon sequence, TEV(tobacco etch virus) protease recognition and cleavage site, AviTag(peptide that allows for enzymatic ...詳細: From aa1209, additional tags are added at the C-terminal, with Foldon sequence, TEV(tobacco etch virus) protease recognition and cleavage site, AviTag(peptide that allows for enzymatic biotinylation),and 6xHis affinity tag. コピー数: 1 / 光学異性体: LEVO
由来(天然)
生物種: Severe acute respiratory syndrome coronavirus 2 (ウイルス)