tetano
Editor, Senior Moderator
Cell Rep Med
. 2021 Jan 19;2(1):100189.
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[SUP] 1 [/SUP], Sierra N Henson[SUP] 2 [/SUP], Annalee S Boyle[SUP] 2 [/SUP], Anna L Engelbrektson[SUP] 2 [/SUP], Zane W Fink[SUP] 1 [/SUP], Fatima Rahee[SUP] 2 [/SUP], Jonathan D'ambrozio[SUP] 3 [/SUP], Kurt E Schaecher[SUP] 3 [/SUP], Mars Stone[SUP] 4 [/SUP], Wenjuan Dong[SUP] 5 [/SUP], Sanjeet Dadwal[SUP] 6 [/SUP], Jianhua Yu[SUP] 5 [/SUP], Michael A Caligiuri[SUP] 5 [/SUP], Piotr Cieplak[SUP] 7 [/SUP], Magnar Bj?r?s[SUP] 8 [/SUP], Mona H Fenstad[SUP] 8 9 [/SUP], Svein A Nordb?[SUP] 8 10 [/SUP], Denis E Kainov[SUP] 8 [/SUP], Norihito Muranaka[SUP] 11 [/SUP], Mark S Chee[SUP] 11 [/SUP], Sergey A Shiryaev[SUP] 7 [/SUP], John A Altin[SUP] 2 [/SUP]
Affiliations
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.
Keywords: SARS-CoV-2; antibody response; cross-reactivity; endemic CoVs; highly multiplexed serology.
. 2021 Jan 19;2(1):100189.
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[SUP] 1 [/SUP], Sierra N Henson[SUP] 2 [/SUP], Annalee S Boyle[SUP] 2 [/SUP], Anna L Engelbrektson[SUP] 2 [/SUP], Zane W Fink[SUP] 1 [/SUP], Fatima Rahee[SUP] 2 [/SUP], Jonathan D'ambrozio[SUP] 3 [/SUP], Kurt E Schaecher[SUP] 3 [/SUP], Mars Stone[SUP] 4 [/SUP], Wenjuan Dong[SUP] 5 [/SUP], Sanjeet Dadwal[SUP] 6 [/SUP], Jianhua Yu[SUP] 5 [/SUP], Michael A Caligiuri[SUP] 5 [/SUP], Piotr Cieplak[SUP] 7 [/SUP], Magnar Bj?r?s[SUP] 8 [/SUP], Mona H Fenstad[SUP] 8 9 [/SUP], Svein A Nordb?[SUP] 8 10 [/SUP], Denis E Kainov[SUP] 8 [/SUP], Norihito Muranaka[SUP] 11 [/SUP], Mark S Chee[SUP] 11 [/SUP], Sergey A Shiryaev[SUP] 7 [/SUP], John A Altin[SUP] 2 [/SUP]
Affiliations
- PMID: 33495758
- PMCID: PMC7816965
- DOI: 10.1016/j.xcrm.2020.100189
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.
Keywords: SARS-CoV-2; antibody response; cross-reactivity; endemic CoVs; highly multiplexed serology.