Epitope-resolved profiling of the SARS-CoV-2 antibody response identifies cross-reactivity with endemic human coronaviruses
| Autor: | Kurt E. Schaecher, Mars Stone, Sierra N. Henson, Wenjuan Dong, Norihito Muranaka, Sergey A. Shiryaev, Jonathan D'ambrozio, John A. Altin, Piotr Cieplak, Jianhua Yu, Mona H. Fenstad, Jason T. Ladner, Sanjeet Dadwal, Magnar Bjørås, Svein Arne Nordbø, Annalee S. Boyle, Michael A. Caligiuri, Anna Engelbrektson, Zane Fink, Mark S. Chee, Fatima Rahee, Denis E. Kainov |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
biology
cross-reactivity SARS-CoV-2 Protein subunit viruses virus diseases antibody response respiratory system biochemical phenomena metabolism and nutrition endemic CoVs medicine.disease_cause Virology Cross-reactivity General Biochemistry Genetics and Molecular Biology Epitope Article respiratory tract diseases Antibody response Antigen highly multiplexed serology Proteome biology.protein Homologous chromosome medicine Antibody |
| Zdroj: | Cell Reports Medicine bioRxiv article-version (status) pre article-version (number) 1 |
| ISSN: | 2666-3791 |
| Popis: | 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. Graphical Abstract Highlights PepSeq enables fully in vitro, highly multiplexed peptide-based antibody assays Epitope mapping shows preexisting antibody reactivity to SARS-CoV-2 antigens Antibodies cross-recognize endemic and pandemic antigens in the Spike S2 subunit Cross-reactive antibodies raised by SARS-CoV-2 preferentially bind endemic homologs Ladner et al. use a fully in vitro, highly multiplexed approach to finely map antibody epitopes across the Spike and Nucleocapsid proteins of all human-infecting coronaviruses. This demonstrates that SARS-CoV-2 elicits antibodies that cross-recognize endemic coronavirus antigens at conserved regions of Spike and that these antibodies preferentially bind endemic homologs. |
| Databáze: | OpenAIRE |
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