Epitope-resolved profiling of the SARS-CoV-2 antibody response identifies cross-reactivity with endemic human coronaviruses

Jason T. Ladner; Sierra N. Henson; Annalee S. Boyle; Anna L. Engelbrektson; Zane W. Fink; Fatima Rahee; Jonathan D'ambrozio; Kurt E. Schaecher; Mars Stone; Wenjuan Dong; Sanjeet Dadwal; Jianhua Yu; Michael A. Caligiuri; Piotr Cieplak; Magnar Bjørås; Mona H. Fenstad; Svein A. Nordbø; Denis E. Kainov; Norihito Muranaka; Mark S. Chee; Sergey A. Shiryaev; John A. Altin

doi:10.1016/j.xcrm.2020.100189

Epitope-resolved profiling of the SARS-CoV-2 antibody response identifies cross-reactivity with endemic human coronaviruses

Jason T. Ladner, Sierra N. Henson, Annalee S. Boyle, Anna L. Engelbrektson, Zane W. Fink, Fatima Rahee, Jonathan D'ambrozio, Kurt E. Schaecher, Mars Stone, Wenjuan Dong, Sanjeet Dadwal, Jianhua Yu, Michael A. Caligiuri, Piotr Cieplak, Magnar Bjørås, Mona H. Fenstad, Svein A. Nordbø, Denis E. Kainov, Norihito Muranaka, Mark S. CheeSergey A. Shiryaev, John A. Altin

Biological Sciences

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

120 Scopus citations

Abstract

The SARS-CoV-2 proteome shares regions of conservation with endemic human coronaviruses (CoVs), but it remains unknown to what extent these may be cross-recognized by the antibody response. Here, we study cross-reactivity using a highly multiplexed peptide assay (PepSeq) to generate an epitope-resolved view of IgG reactivity across all human CoVs in both COVID-19 convalescent and negative donors. PepSeq resolves epitopes across the SARS-CoV-2 Spike and Nucleocapsid proteins that are commonly targeted in convalescent donors, including several sites also recognized in some uninfected controls. By comparing patterns of homologous reactivity between CoVs and using targeted antibody-depletion experiments, we demonstrate that SARS-CoV-2 elicits antibodies that cross-recognize pandemic and endemic CoV antigens at two Spike S2 subunit epitopes. We further show that these cross-reactive antibodies preferentially bind endemic homologs. Our findings highlight sites at which the SARS-CoV-2 response appears to be shaped by previous CoV exposures and which have the potential to raise broadly neutralizing responses.

Original language	English (US)
Article number	100189
Journal	Cell Reports Medicine
Volume	2
Issue number	1
DOIs	https://doi.org/10.1016/j.xcrm.2020.100189
State	Published - Jan 19 2021

Keywords

SARS-CoV-2
antibody response
cross-reactivity
endemic CoVs
highly multiplexed serology

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.xcrm.2020.100189

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Ladner, J. T., Henson, S. N., Boyle, A. S., Engelbrektson, A. L., Fink, Z. W., Rahee, F., D'ambrozio, J., Schaecher, K. E., Stone, M., Dong, W., Dadwal, S., Yu, J., Caligiuri, M. A., Cieplak, P., Bjørås, M., Fenstad, M. H., Nordbø, S. A., Kainov, D. E., Muranaka, N., ... Altin, J. A. (2021). Epitope-resolved profiling of the SARS-CoV-2 antibody response identifies cross-reactivity with endemic human coronaviruses. Cell Reports Medicine, 2(1), Article 100189. https://doi.org/10.1016/j.xcrm.2020.100189

Ladner, JT, Henson, SN, Boyle, AS, Engelbrektson, AL, Fink, ZW, Rahee, F, D'ambrozio, J, Schaecher, KE, Stone, M, Dong, W, Dadwal, S, Yu, J, Caligiuri, MA, Cieplak, P, Bjørås, M, Fenstad, MH, Nordbø, SA, Kainov, DE, Muranaka, N, Chee, MS, Shiryaev, SA & Altin, JA 2021, 'Epitope-resolved profiling of the SARS-CoV-2 antibody response identifies cross-reactivity with endemic human coronaviruses', Cell Reports Medicine, vol. 2, no. 1, 100189. https://doi.org/10.1016/j.xcrm.2020.100189

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title = "Epitope-resolved profiling of the SARS-CoV-2 antibody response identifies cross-reactivity with endemic human coronaviruses",

abstract = "The SARS-CoV-2 proteome shares regions of conservation with endemic human coronaviruses (CoVs), but it remains unknown to what extent these may be cross-recognized by the antibody response. Here, we study cross-reactivity using a highly multiplexed peptide assay (PepSeq) to generate an epitope-resolved view of IgG reactivity across all human CoVs in both COVID-19 convalescent and negative donors. PepSeq resolves epitopes across the SARS-CoV-2 Spike and Nucleocapsid proteins that are commonly targeted in convalescent donors, including several sites also recognized in some uninfected controls. By comparing patterns of homologous reactivity between CoVs and using targeted antibody-depletion experiments, we demonstrate that SARS-CoV-2 elicits antibodies that cross-recognize pandemic and endemic CoV antigens at two Spike S2 subunit epitopes. We further show that these cross-reactive antibodies preferentially bind endemic homologs. Our findings highlight sites at which the SARS-CoV-2 response appears to be shaped by previous CoV exposures and which have the potential to raise broadly neutralizing responses.",

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doi = "10.1016/j.xcrm.2020.100189",

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AU - Ladner, Jason T.

AU - Henson, Sierra N.

AU - Boyle, Annalee S.

AU - Engelbrektson, Anna L.

AU - Fink, Zane W.

AU - Rahee, Fatima

AU - D'ambrozio, Jonathan

AU - Schaecher, Kurt E.

AU - Stone, Mars

AU - Dong, Wenjuan

AU - Dadwal, Sanjeet

AU - Yu, Jianhua

AU - Caligiuri, Michael A.

AU - Cieplak, Piotr

AU - Bjørås, Magnar

AU - Fenstad, Mona H.

AU - Nordbø, Svein A.

AU - Kainov, Denis E.

AU - Muranaka, Norihito

AU - Chee, Mark S.

AU - Shiryaev, Sergey A.

AU - Altin, John A.

PY - 2021/1/19

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N2 - The SARS-CoV-2 proteome shares regions of conservation with endemic human coronaviruses (CoVs), but it remains unknown to what extent these may be cross-recognized by the antibody response. Here, we study cross-reactivity using a highly multiplexed peptide assay (PepSeq) to generate an epitope-resolved view of IgG reactivity across all human CoVs in both COVID-19 convalescent and negative donors. PepSeq resolves epitopes across the SARS-CoV-2 Spike and Nucleocapsid proteins that are commonly targeted in convalescent donors, including several sites also recognized in some uninfected controls. By comparing patterns of homologous reactivity between CoVs and using targeted antibody-depletion experiments, we demonstrate that SARS-CoV-2 elicits antibodies that cross-recognize pandemic and endemic CoV antigens at two Spike S2 subunit epitopes. We further show that these cross-reactive antibodies preferentially bind endemic homologs. Our findings highlight sites at which the SARS-CoV-2 response appears to be shaped by previous CoV exposures and which have the potential to raise broadly neutralizing responses.

AB - The SARS-CoV-2 proteome shares regions of conservation with endemic human coronaviruses (CoVs), but it remains unknown to what extent these may be cross-recognized by the antibody response. Here, we study cross-reactivity using a highly multiplexed peptide assay (PepSeq) to generate an epitope-resolved view of IgG reactivity across all human CoVs in both COVID-19 convalescent and negative donors. PepSeq resolves epitopes across the SARS-CoV-2 Spike and Nucleocapsid proteins that are commonly targeted in convalescent donors, including several sites also recognized in some uninfected controls. By comparing patterns of homologous reactivity between CoVs and using targeted antibody-depletion experiments, we demonstrate that SARS-CoV-2 elicits antibodies that cross-recognize pandemic and endemic CoV antigens at two Spike S2 subunit epitopes. We further show that these cross-reactive antibodies preferentially bind endemic homologs. Our findings highlight sites at which the SARS-CoV-2 response appears to be shaped by previous CoV exposures and which have the potential to raise broadly neutralizing responses.

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Epitope-resolved profiling of the SARS-CoV-2 antibody response identifies cross-reactivity with endemic human coronaviruses

Abstract

Keywords

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