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タイトル | Potent neutralizing broad-spectrum antibody against SARS-CoV-2 generated from dual-antigen-specific B cells from convalescents. |
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ジャーナル・号・ページ | iScience, Vol. 26, Issue 6, Page 106955, Year 2023 |
掲載日 | 2023年6月16日 |
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 / / |
PubMed 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. |
リンク | iScience / PubMed:37288342 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.3 - 4.4 Å |
構造データ | EMDB-33065, PDB-7x93: EMDB-33066, PDB-7x94: EMDB-33067, PDB-7x95: EMDB-33068, PDB-7x96: EMDB-33643, PDB-7y6l: EMDB-33644, PDB-7y6n: |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | VIRAL PROTEIN / severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike trimer / COVID-19 / human neutralizing antibody / RBD |