Reduced B cell antigenicity of Omicron lowers host serologic response

Jérôme Tubiana; Yufei Xiang; Li Fan; Haim J. Wolfson; Kong Chen; Dina Schneidman-Duhovny; Yi Shi

doi:10.1016/j.celrep.2022.111512

Reduced B cell antigenicity of Omicron lowers host serologic response

Jérôme Tubiana, Yufei Xiang, Li Fan, Haim J. Wolfson, Kong Chen^*, Dina Schneidman-Duhovny^*, Yi Shi^*

^*Corresponding author for this work

The Rachel and Selim Benin School of Engineering and Computer Science

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

The SARS-CoV-2 Omicron variant evades most neutralizing vaccine-induced antibodies and is associated with lower antibody titers upon breakthrough infections than previous variants. However, the mechanism remains unclear. Here, we find using a geometric deep-learning model that Omicron's extensively mutated receptor binding site (RBS) features reduced antigenicity compared with previous variants. Mice immunization experiments with different recombinant receptor binding domain (RBD) variants confirm that the serological response to Omicron is drastically attenuated and less potent. Analyses of serum cross-reactivity and competitive ELISA reveal a reduction in antibody response across both variable and conserved RBD epitopes. Computational modeling confirms that the RBS has a potential for further antigenicity reduction while retaining efficient receptor binding. Finally, we find a similar trend of antigenicity reduction over decades for hCoV229E, a common cold coronavirus. Thus, our study explains the reduced antibody titers associated with Omicron infection and reveals a possible trajectory of future viral evolution.

Original language	American English
Article number	111512
Journal	Cell Reports
Volume	41
Issue number	3
DOIs	https://doi.org/10.1016/j.celrep.2022.111512
State	Published - 18 Oct 2022

Bibliographical note

Funding Information:
We thank Zhe Sang for the analysis of antibody binding. J.T. acknowledges helpful discussion with Andrea Di Gioacchino and Simona Cocco. Funding: This work was supported by NIH grants R35GM137905 (Y.S.), R01AI163011 (Y.S. and D.S.), R01HL137709 (K.C.), ISF 1466/18 and Israeli Ministry of Science and Technology (D.S.), the Edmond J. Safra Center for Bioinformatics at Tel Aviv University, the Human Frontier Science Program (cross-disciplinary postdoctoral fellowship LT001058/2019-C ) (J.T.), and Len Blavatnik and the Blavatnik Family Foundation (H.J.W.).

Publisher Copyright:
© 2022

Keywords

CP: Immunology
CP: Microbiology
Omicron variant of concern
SARS-CoV-2
antigenicity
computational structural biology
deep learning
spike protein

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.celrep.2022.111512

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title = "Reduced B cell antigenicity of Omicron lowers host serologic response",

abstract = "The SARS-CoV-2 Omicron variant evades most neutralizing vaccine-induced antibodies and is associated with lower antibody titers upon breakthrough infections than previous variants. However, the mechanism remains unclear. Here, we find using a geometric deep-learning model that Omicron's extensively mutated receptor binding site (RBS) features reduced antigenicity compared with previous variants. Mice immunization experiments with different recombinant receptor binding domain (RBD) variants confirm that the serological response to Omicron is drastically attenuated and less potent. Analyses of serum cross-reactivity and competitive ELISA reveal a reduction in antibody response across both variable and conserved RBD epitopes. Computational modeling confirms that the RBS has a potential for further antigenicity reduction while retaining efficient receptor binding. Finally, we find a similar trend of antigenicity reduction over decades for hCoV229E, a common cold coronavirus. Thus, our study explains the reduced antibody titers associated with Omicron infection and reveals a possible trajectory of future viral evolution.",

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note = "Funding Information: We thank Zhe Sang for the analysis of antibody binding. J.T. acknowledges helpful discussion with Andrea Di Gioacchino and Simona Cocco. Funding: This work was supported by NIH grants R35GM137905 (Y.S.), R01AI163011 (Y.S. and D.S.), R01HL137709 (K.C.), ISF 1466/18 and Israeli Ministry of Science and Technology (D.S.), the Edmond J. Safra Center for Bioinformatics at Tel Aviv University, the Human Frontier Science Program (cross-disciplinary postdoctoral fellowship LT001058/2019-C ) (J.T.), and Len Blavatnik and the Blavatnik Family Foundation (H.J.W.). Publisher Copyright: {\textcopyright} 2022",

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AU - Tubiana, Jérôme

AU - Xiang, Yufei

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AU - Wolfson, Haim J.

AU - Chen, Kong

AU - Schneidman-Duhovny, Dina

AU - Shi, Yi

N1 - Funding Information: We thank Zhe Sang for the analysis of antibody binding. J.T. acknowledges helpful discussion with Andrea Di Gioacchino and Simona Cocco. Funding: This work was supported by NIH grants R35GM137905 (Y.S.), R01AI163011 (Y.S. and D.S.), R01HL137709 (K.C.), ISF 1466/18 and Israeli Ministry of Science and Technology (D.S.), the Edmond J. Safra Center for Bioinformatics at Tel Aviv University, the Human Frontier Science Program (cross-disciplinary postdoctoral fellowship LT001058/2019-C ) (J.T.), and Len Blavatnik and the Blavatnik Family Foundation (H.J.W.). Publisher Copyright: © 2022

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N2 - The SARS-CoV-2 Omicron variant evades most neutralizing vaccine-induced antibodies and is associated with lower antibody titers upon breakthrough infections than previous variants. However, the mechanism remains unclear. Here, we find using a geometric deep-learning model that Omicron's extensively mutated receptor binding site (RBS) features reduced antigenicity compared with previous variants. Mice immunization experiments with different recombinant receptor binding domain (RBD) variants confirm that the serological response to Omicron is drastically attenuated and less potent. Analyses of serum cross-reactivity and competitive ELISA reveal a reduction in antibody response across both variable and conserved RBD epitopes. Computational modeling confirms that the RBS has a potential for further antigenicity reduction while retaining efficient receptor binding. Finally, we find a similar trend of antigenicity reduction over decades for hCoV229E, a common cold coronavirus. Thus, our study explains the reduced antibody titers associated with Omicron infection and reveals a possible trajectory of future viral evolution.

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Reduced B cell antigenicity of Omicron lowers host serologic response

Abstract

Bibliographical note

Keywords

UN SDGs

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