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

Cell Rep Med. 2021 Jan 19;2(1):100189. doi: 10.1016/j.xcrm.2020.100189.

Authors

Jason T Ladner¹, Sierra N Henson², Annalee S Boyle², Anna L Engelbrektson², Zane W Fink¹, Fatima Rahee², Jonathan D'ambrozio³, Kurt E Schaecher³, Mars Stone⁴, Wenjuan Dong⁵, Sanjeet Dadwal⁶, Jianhua Yu⁵, Michael A Caligiuri⁵, Piotr Cieplak⁷, Magnar Bjørås⁸, Mona H Fenstad^{8

9}, Svein A Nordbø^{8

10}, Denis E Kainov⁸, Norihito Muranaka¹¹, Mark S Chee¹¹, Sergey A Shiryaev⁷, John A Altin²

Affiliations

¹ The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, USA.
² The Translational Genomics Research Institute (TGen), Phoenix and Flagstaff, AZ, USA.
³ Walter Reed National Military Medical Center, Bethesda, MD, USA.
⁴ Vitalant Research Institute and Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.
⁵ Hematologic Malignancies and Stem Cell Transplantation Institute, City of Hope National Medical Center, Duarte, CA, USA.
⁶ Division of Infectious Diseases, City of Hope National Medical Center, Duarte, CA, USA.
⁷ Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
⁸ Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
⁹ Department of Immunology and Transfusion Medicine, St. Olavs Hospital, Trondheim, Norway.
¹⁰ Department of Medical Microbiology, St. Olavs Hospital, Trondheim, Norway.
¹¹ Encodia, San Diego, CA, USA.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Abstract

Publication types

Grants and funding