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Germinal center-derived broadly neutralizing antibodies adapt to SARS-CoV-2 antigenic drift

Kiyomi Shitaoka, View ORCID ProfileYohei Kawano, Akifumi Higashiura, View ORCID ProfileYoko Mizoguchi, View ORCID ProfileTakao Hashiguchi, Norihisa Nishimichi, Shiyu Huang, Ayano Ito, Akima Yamamoto, View ORCID ProfileShun Ohki, Miyuki Kanda, Tomohiro Taniguchi, Yasuyuki Yokosaki, View ORCID ProfileSatoshi Okada, View ORCID ProfileTakemasa Sakaguchi, View ORCID ProfileTomoharu Yasuda
doi: https://doi.org/10.1101/2022.01.26.477937
Kiyomi Shitaoka
1Department of Immunology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan
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Yohei Kawano
1Department of Immunology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan
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Akifumi Higashiura
2Department of Virology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan
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Yoko Mizoguchi
3Department of Pediatrics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan
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Takao Hashiguchi
4Laboratory of Medical Virology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan
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Norihisa Nishimichi
5Integrin-Matrix Biomedical Science, Translational Research Center, Hiroshima University, Hiroshima, 734-8551, Japan
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Shiyu Huang
1Department of Immunology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan
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Ayano Ito
1Department of Immunology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan
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Akima Yamamoto
2Department of Virology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan
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Shun Ohki
1Department of Immunology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan
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Miyuki Kanda
6Collaborative laboratory of Liquid Biopsy, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan
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Tomohiro Taniguchi
7Division of General Internal Medicine and Infectious Diseases, Hiroshima Prefectural Hospital, Hiroshima, 734-8530
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Yasuyuki Yokosaki
5Integrin-Matrix Biomedical Science, Translational Research Center, Hiroshima University, Hiroshima, 734-8551, Japan
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Satoshi Okada
3Department of Pediatrics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan
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Takemasa Sakaguchi
2Department of Virology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan
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Tomoharu Yasuda
1Department of Immunology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan
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  • ORCID record for Tomoharu Yasuda
  • For correspondence: yasudat@hiroshima-u.ac.jp
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Abstract

The outbreak of SARS-CoV-2 variant Omicron which harbors a striking number of mutations in the spike protein has been raising concerns about the effectiveness of vaccines and antibody treatment1. Here, we confirmed a substantial reduction in neutralizing potency against Omicron in all convalescent and vaccinated sera. However, we found that some people infected by the early strain show relatively higher neutralization to Omicron. From those B cells, we developed neutralizing antibodies inhibiting broad variants including Delta and Omicron. Unlike reported antibodies, one had an extremely large interface and widely covered receptor binding motif of spike, thereby interfering with diversified variants. Somatic mutations introduced by long-term germinal center reaction contributed to the key structure of antibodies and the universal interaction with spike variants. Recalling such rare B cells may confer sustainable protection against SARS-CoV-2 variants emerging one after another.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted January 27, 2022.
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Germinal center-derived broadly neutralizing antibodies adapt to SARS-CoV-2 antigenic drift
Kiyomi Shitaoka, Yohei Kawano, Akifumi Higashiura, Yoko Mizoguchi, Takao Hashiguchi, Norihisa Nishimichi, Shiyu Huang, Ayano Ito, Akima Yamamoto, Shun Ohki, Miyuki Kanda, Tomohiro Taniguchi, Yasuyuki Yokosaki, Satoshi Okada, Takemasa Sakaguchi, Tomoharu Yasuda
bioRxiv 2022.01.26.477937; doi: https://doi.org/10.1101/2022.01.26.477937
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Germinal center-derived broadly neutralizing antibodies adapt to SARS-CoV-2 antigenic drift
Kiyomi Shitaoka, Yohei Kawano, Akifumi Higashiura, Yoko Mizoguchi, Takao Hashiguchi, Norihisa Nishimichi, Shiyu Huang, Ayano Ito, Akima Yamamoto, Shun Ohki, Miyuki Kanda, Tomohiro Taniguchi, Yasuyuki Yokosaki, Satoshi Okada, Takemasa Sakaguchi, Tomoharu Yasuda
bioRxiv 2022.01.26.477937; doi: https://doi.org/10.1101/2022.01.26.477937

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