@article{204a83be6476409aa04aac8c92355282,
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.",
keywords = "SARS-CoV-2, antibody response, cross-reactivity, endemic CoVs, highly multiplexed serology",
author = "Ladner, {Jason T.} and Henson, {Sierra N.} and Boyle, {Annalee S.} and Engelbrektson, {Anna L.} and Fink, {Zane W.} and Fatima Rahee and Jonathan D'ambrozio and Schaecher, {Kurt E.} and Mars Stone and Wenjuan Dong and Sanjeet Dadwal and Jianhua Yu and Caligiuri, {Michael A.} and Piotr Cieplak and Magnar Bj{\o}r{\aa}s and Fenstad, {Mona H.} and Nordb{\o}, {Svein A.} and Kainov, {Denis E.} and Norihito Muranaka and Chee, {Mark S.} and Shiryaev, {Sergey A.} and Altin, {John A.}",
note = "Funding Information: This work was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award nos. U24AI152172 and U24AI152172-01S1 ; the National Institute on Minority Health and Health Disparities of the National Institutes of Health under award no. U54MD012388 ; and the State of Arizona Technology and Research Initiative Fund (TRIF), administered by the Arizona Board of Regents , through Northern Arizona University . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Z.W.F. was supported by a Hooper Undergraduate Research Award and a Jean Shuler Research Mini-Grant . We are grateful for assistance from Mike Busch and Phillip Williamson in obtaining samples and Piotr Swiderski in synthesizing a custom oligonucleotide reagent. We are also grateful for the constructive feedback received from Paul Keim, Stephen Daley, Gerard Zurawski, and Erik Settles, which greatly improved the manuscript. Publisher Copyright: {\textcopyright} 2020 The Author(s)",
year = "2021",
month = jan,
day = "19",
doi = "10.1016/j.xcrm.2020.100189",
language = "English (US)",
volume = "2",
journal = "Cell Reports Medicine",
issn = "2666-3791",
publisher = "Cell Press",
number = "1",
}