EBioMedicine (Dec 2024)
Induction of IGHV3-53 public antibodies with broadly neutralising activity against SARS-CoV-2 including Omicron subvariants in a Delta breakthrough infection caseResearch in context
- Takeo Kuwata,
- Yu Kaku,
- Shashwata Biswas,
- Kaho Matsumoto,
- Mikiko Shimizu,
- Yoko Kawanami,
- Ryuta Uraki,
- Kyo Okazaki,
- Rumi Minami,
- Yoji Nagasaki,
- Mami Nagashima,
- Isao Yoshida,
- Kenji Sadamasu,
- Kazuhisa Yoshimura,
- Mutsumi Ito,
- Maki Kiso,
- Seiya Yamayoshi,
- Masaki Imai,
- Terumasa Ikeda,
- Kei Sato,
- Mako Toyoda,
- Takamasa Ueno,
- Takako Inoue,
- Yasuhito Tanaka,
- Kanako Tarakado Kimura,
- Takao Hashiguchi,
- Yukihiko Sugita,
- Takeshi Noda,
- Hiroshi Morioka,
- Yoshihiro Kawaoka,
- Shuzo Matsushita,
- Jumpei Ito,
- Naoko Misawa,
- Arnon Plianchaisuk,
- Ziyi Guo,
- Alfredo Hina, Jr.,
- Keiya Uriu,
- Kaoru Usui,
- Wilaiporn Saikruang,
- Spyridon Lytras,
- Ryo Yoshimura,
- Shusuke Kawakubo,
- Luca Nishimura,
- Yusuke Kosugi,
- Shigeru Fujita,
- Luo Chen,
- Jarel Elgin M. Tolentino,
- Lin Pan,
- Wenye Li,
- Maximilian Stanley Yo,
- Kio Horinaka,
- Mai Suganami,
- Adam P. Strange,
- Mika Chiba,
- Keiko Iida,
- Naomi Ohsumi,
- Kaho Okumura,
- Shiho Tanaka,
- Eiko Ogawa,
- Kyoko Yasuda,
- Tsuki Fukuda,
- Rina Osujo,
- Takasuke Fukuhara,
- Tomokazu Tamura,
- Rigel Suzuki,
- Saori Suzuki,
- Hayato Ito,
- Keita Matsuno,
- Hirofumi Sawa,
- Naganori Nao,
- Shinya Tanaka,
- Masumi Tsuda,
- Lei Wang,
- Yoshikata Oda,
- Zannatul Ferdous,
- Kenji Shishido,
- Keita Mizuma,
- Isshu Kojima,
- Jingshu Li,
- Tomoya Tsubo,
- Shuhei Tsujino,
- So Nakagawa,
- Kotaro Shirakawa,
- Akifumi Takaori-Kondo,
- Kayoko Nagata,
- Ryosuke Nomura,
- Yoshihito Horisawa,
- Yusuke Tashiro,
- Yugo Kawai,
- Kazuo Takayama,
- Rina Hashimoto,
- Sayaka Deguchi,
- Yukio Watanabe,
- Ayaka Sakamoto,
- Naoko Yasuhara,
- Tateki Suzuki,
- Kanako Kimura,
- Jiei Sasaki,
- Yukari Nakajima,
- Hisano Yajima,
- Yoshitaka Nakata,
- Hiroki Futatsusako,
- Takashi Irie,
- Ryoko Kawabata,
- Kaori Tabata,
- Hesham Nasser,
- Ryo Shimizu,
- MST Monira Begum,
- Michael Jonathan,
- Yuka Mugita,
- Otowa Takahashi,
- Kimiko Ichihara,
- Chihiro Motozono,
- Sharee Leong,
- Akatsuki Saito,
- Maya Shofa,
- Yuki Shibatani,
- Tomoko Nishiuchi,
- Hiroyuki Asakura,
- Jiri Zahradnik,
- Prokopios Andrikopoulos,
- Miguel Padilla-Blanco,
- Aditi Konar
Affiliations
- Takeo Kuwata
- Collaborative Research Program with the Chemo-Sero-Therapeutic Research Institute for Anti-viral Agents and Hematological Diseases, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan; Corresponding author. Joint Research Center for Human Retrovirus infection, Kumamoto University, 5-1 Oe Honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
- Yu Kaku
- Collaborative Research Program with the Chemo-Sero-Therapeutic Research Institute for Anti-viral Agents and Hematological Diseases, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan; Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
- Shashwata Biswas
- Collaborative Research Program with the Chemo-Sero-Therapeutic Research Institute for Anti-viral Agents and Hematological Diseases, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan
- Kaho Matsumoto
- Collaborative Research Program with the Chemo-Sero-Therapeutic Research Institute for Anti-viral Agents and Hematological Diseases, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan
- Mikiko Shimizu
- Collaborative Research Program with the Chemo-Sero-Therapeutic Research Institute for Anti-viral Agents and Hematological Diseases, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan
- Yoko Kawanami
- Collaborative Research Program with the Chemo-Sero-Therapeutic Research Institute for Anti-viral Agents and Hematological Diseases, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan
- Ryuta Uraki
- Division of Virology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
- Kyo Okazaki
- Department of Analytical and Biophysical Chemistry, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan
- Rumi Minami
- Internal Medicine, Clinical Research Institute, NHO Kyushu Medical Center, Fukuoka, Japan
- Yoji Nagasaki
- Internal Medicine, Clinical Research Institute, NHO Kyushu Medical Center, Fukuoka, Japan
- Mami Nagashima
- Tokyo Metropolitan Institute of Public Health, Tokyo, Japan
- Isao Yoshida
- Tokyo Metropolitan Institute of Public Health, Tokyo, Japan
- Kenji Sadamasu
- Tokyo Metropolitan Institute of Public Health, Tokyo, Japan
- Kazuhisa Yoshimura
- Tokyo Metropolitan Institute of Public Health, Tokyo, Japan
- Mutsumi Ito
- Division of Virology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
- Maki Kiso
- Division of Virology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
- Seiya Yamayoshi
- Division of Virology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
- Masaki Imai
- Division of Virology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
- Terumasa Ikeda
- Division of Molecular Virology and Genetics, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan
- Kei Sato
- Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
- Mako Toyoda
- Division of Infection and Immunity, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan
- Takamasa Ueno
- Division of Infection and Immunity, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan
- Takako Inoue
- Department of Clinical Laboratory Medicine, Nagoya City University Hospital, Nagoya, Japan
- Yasuhito Tanaka
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
- Kanako Tarakado Kimura
- Laboratory of Medical Virology, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan
- Takao Hashiguchi
- Laboratory of Medical Virology, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan
- Yukihiko Sugita
- Laboratory of Ultrastructural Virology, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan
- Takeshi Noda
- Laboratory of Ultrastructural Virology, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan
- Hiroshi Morioka
- Department of Analytical and Biophysical Chemistry, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan
- Yoshihiro Kawaoka
- Division of Virology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
- Shuzo Matsushita
- Collaborative Research Program with the Chemo-Sero-Therapeutic Research Institute for Anti-viral Agents and Hematological Diseases, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan; Corresponding author. Joint Research Center for Human Retrovirus infection, Kumamoto University, 5-1 Oe Honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
- Jumpei Ito
- Naoko Misawa
- Arnon Plianchaisuk
- Ziyi Guo
- Alfredo Hina, Jr.
- Keiya Uriu
- Kaoru Usui
- Wilaiporn Saikruang
- Spyridon Lytras
- Ryo Yoshimura
- Shusuke Kawakubo
- Luca Nishimura
- Yusuke Kosugi
- Shigeru Fujita
- Luo Chen
- Jarel Elgin M. Tolentino
- Lin Pan
- Wenye Li
- Maximilian Stanley Yo
- Kio Horinaka
- Mai Suganami
- Adam P. Strange
- Mika Chiba
- Keiko Iida
- Naomi Ohsumi
- Kaho Okumura
- Shiho Tanaka
- Eiko Ogawa
- Kyoko Yasuda
- Tsuki Fukuda
- Rina Osujo
- Takasuke Fukuhara
- Tomokazu Tamura
- Rigel Suzuki
- Saori Suzuki
- Hayato Ito
- Keita Matsuno
- Hirofumi Sawa
- Naganori Nao
- Shinya Tanaka
- Masumi Tsuda
- Lei Wang
- Yoshikata Oda
- Zannatul Ferdous
- Kenji Shishido
- Keita Mizuma
- Isshu Kojima
- Jingshu Li
- Tomoya Tsubo
- Shuhei Tsujino
- So Nakagawa
- Kotaro Shirakawa
- Akifumi Takaori-Kondo
- Kayoko Nagata
- Ryosuke Nomura
- Yoshihito Horisawa
- Yusuke Tashiro
- Yugo Kawai
- Kazuo Takayama
- Rina Hashimoto
- Sayaka Deguchi
- Yukio Watanabe
- Ayaka Sakamoto
- Naoko Yasuhara
- Tateki Suzuki
- Kanako Kimura
- Jiei Sasaki
- Yukari Nakajima
- Hisano Yajima
- Yoshitaka Nakata
- Hiroki Futatsusako
- Takashi Irie
- Ryoko Kawabata
- Kaori Tabata
- Hesham Nasser
- Ryo Shimizu
- MST Monira Begum
- Michael Jonathan
- Yuka Mugita
- Otowa Takahashi
- Kimiko Ichihara
- Chihiro Motozono
- Sharee Leong
- Akatsuki Saito
- Maya Shofa
- Yuki Shibatani
- Tomoko Nishiuchi
- Hiroyuki Asakura
- Jiri Zahradnik
- Prokopios Andrikopoulos
- Miguel Padilla-Blanco
- Aditi Konar
- Journal volume & issue
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Vol. 110
p. 105439
Abstract
Summary: Background: Emergence of SARS-CoV-2 variants that escape neutralising antibodies hampers the development of vaccines and therapeutic antibodies against SARS-CoV-2. IGHV3-53/3-66-derived public antibodies, which are generally specific to the prototype virus and are frequently induced in infected or vaccinated individuals, show minimal affinity maturation and high potency against prototype SARS-CoV-2. Methods: Monoclonal antibodies isolated from a Delta breakthrough infection case were analysed for cross-neutralising activities against SARS-CoV-2 variants. The broadly neutralising antibody K4-66 was further analysed in a hamster model, and the effect of somatic hypermutations was assessed using the inferred germline precursor. Findings: Antibodies derived from IGHV3-53/3-66 showed broader neutralising activity than antibodies derived from IGHV1-69 and other IGHV genes. IGHV3-53/3-66 antibodies neutralised the Delta variant better than the IGHV1-69 antibodies, suggesting that the IGHV3-53/3-66 antibodies were further maturated by Delta breakthrough infection. One IGHV3-53/3-66 antibody, K4-66, neutralised all Omicron subvariants tested, including EG.5.1, BA.2.86, and JN.1, and decreased the viral load in the lungs of hamsters infected with Omicron subvariant XBB.1.5. The importance of somatic hypermutations was demonstrated by the loss of neutralising activity of the inferred germline precursor of K4-66 against Beta and Omicron variants. Interpretation: Broadly neutralising IGHV3-53/3-66 antibodies have potential as a target for the development of effective vaccines and therapeutic antibodies against newly emerging SARS-CoV-2 variants. Funding: This work was supported by grants from AMED (JP23ym0126048, JP22ym0126048, JP21ym0126048, JP23wm0125002, JP233fa627001, JP223fa627009, JP24jf0126002, and JP22fk0108572), and the JSPS (JP21H02970, JK23K20041, and JPJSCCA20240006).
