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Neutralization sensitivity of Omicron BA.2.75 to therapeutic monoclonal antibodies

Daichi Yamasoba, Izumi Kimura, Yusuke Kosugi, Keiya Uriu, Shigeru Fujita, Jumpei Ito, View ORCID ProfileKei Sato, The Genotype to Phenotype Japan (G2P-Japan) Consortium
doi: https://doi.org/10.1101/2022.07.14.500041
Daichi Yamasoba
1The University of Tokyo, Tokyo, Japan
2Kobe University, Hyogo, Japan
Ph.D.
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Izumi Kimura
1The University of Tokyo, Tokyo, Japan
Ph.D.
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Yusuke Kosugi
1The University of Tokyo, Tokyo, Japan
M.S.
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Keiya Uriu
1The University of Tokyo, Tokyo, Japan
M.S.
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Shigeru Fujita
1The University of Tokyo, Tokyo, Japan
D.V.M.
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Jumpei Ito
1The University of Tokyo, Tokyo, Japan
D.V.M., Ph.D.
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Kei Sato
1The University of Tokyo, Tokyo, Japan
Ph.D.
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  • ORCID record for Kei Sato
  • For correspondence: KeiSato@g.ecc.u-tokyo.ac.jp
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Abstract

Since the end of 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant outcompeted other variants and took over the world. After the emergence of original Omicron BA.1, Omicron BA.2 subvariant emerged and outcompeted BA.1. As of July 2022, some BA.2 subvariants, including BA.2.12.1, BA.4 and BA.5, emerged in multiple countries and begun outcompeting original BA.2. Moreover, a novel BA.2 subvariant, BA.2.75, was detected in eight countries including India at the end of June 2022, and preliminary investigations suggest that BA.2.75 is more transmissible over the other BA.2 subvariants. On July 7, 2022, the WHO classified BA.2.75 as a variant-of-concern lineage under monitoring. We have recently demonstrated that BA.4/5 is highly resistant to a therapeutic monoclonal antibody, cilgavimab, than BA.2. The resistance of SARS-CoV-2 variants to therapeutic antibodies can be attributed to the mutations in the viral spike protein. Compared to the BA.2 spike, BA.2.12.1 and BA.4/5 respectively bear two and four mutations in their spike proteins. On the other hand, the majority of BA.2.75 spike bears nine substitutions. The fact that the mutation number in the BA.2.75 spike is larger than those in the BA.4/5 spike raises the possibility that the BA.2.75 spike significantly reduces sensitivity towards therapeutic monoclonal antibodies than BA.2 and BA.4/5. In this study, we generated pseudoviruses harboring the spike proteins of BA.2.75, BA.4/5 and BA.2 and evaluated the efficacy of ten therapeutic monoclonal antibodies and three antibody cocktails against BA.2.75.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Conflict of interest: The authors declare that no competing interests exist.

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 July 15, 2022.
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Neutralization sensitivity of Omicron BA.2.75 to therapeutic monoclonal antibodies
Daichi Yamasoba, Izumi Kimura, Yusuke Kosugi, Keiya Uriu, Shigeru Fujita, Jumpei Ito, Kei Sato, The Genotype to Phenotype Japan (G2P-Japan) Consortium
bioRxiv 2022.07.14.500041; doi: https://doi.org/10.1101/2022.07.14.500041
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Neutralization sensitivity of Omicron BA.2.75 to therapeutic monoclonal antibodies
Daichi Yamasoba, Izumi Kimura, Yusuke Kosugi, Keiya Uriu, Shigeru Fujita, Jumpei Ito, Kei Sato, The Genotype to Phenotype Japan (G2P-Japan) Consortium
bioRxiv 2022.07.14.500041; doi: https://doi.org/10.1101/2022.07.14.500041

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