Japan Agency for Medical Research and Development (AMED)
JP21ym0126022
日本
引用
ジャーナル: iScience / 年: 2023 タイトル: Potent neutralizing broad-spectrum antibody against SARS-CoV-2 generated from dual-antigen-specific B cells from convalescents. 著者: Masaru Takeshita / Hidehiro Fukuyama / Katsuhiko Kamada / Takehisa Matsumoto / Chieko Makino-Okamura / Qingshun Lin / Machie Sakuma / Eiki Kawahara / Isato Yamazaki / Tomomi Uchikubo-Kamo / ...著者: 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 / / 要旨: 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 ...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.
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 Ab712
要素
複合体: The SARS-CoV-2 spike protein bound with the Fab fragment of a human neutralizing antibody Ab712
タンパク質・ペプチド: Spike glycoprotein
タンパク質・ペプチド: Ab712 heavy chain
タンパク質・ペプチド: Ab712 light chain
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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 Ab712 タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all
由来(天然)
生物種: Homo sapiens (ヒト)
分子量
理論値: 560 KDa
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分子 #1: Spike glycoprotein
分子
名称: Spike glycoprotein / タイプ: protein_or_peptide / ID: 1 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)