High-resolution analysis of long-term serum antibodies in humans following convalescence of SARS-CoV-2 infection

Abstract Long-term antibody responses to SARS-CoV-2 have focused on responses to full-length spike protein, specific domains within spike, or nucleoprotein. In this study, we used high-density peptide microarrays representing the complete proteome of SARS-CoV-2 to identify binding sites (epitopes) t...

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Main Authors: Antonio Facciuolo, Erin Scruten, Sean Lipsit, Amanda Lang, Zoë Parker Cates, Jocelyne M. Lew, Darryl Falzarano, Volker Gerdts, Anthony J. Kusalik, Scott Napper
Format: Article
Language:English
Published: Nature Portfolio 2022-05-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-12032-8
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author Antonio Facciuolo
Erin Scruten
Sean Lipsit
Amanda Lang
Zoë Parker Cates
Jocelyne M. Lew
Darryl Falzarano
Volker Gerdts
Anthony J. Kusalik
Scott Napper
author_facet Antonio Facciuolo
Erin Scruten
Sean Lipsit
Amanda Lang
Zoë Parker Cates
Jocelyne M. Lew
Darryl Falzarano
Volker Gerdts
Anthony J. Kusalik
Scott Napper
author_sort Antonio Facciuolo
collection DOAJ
description Abstract Long-term antibody responses to SARS-CoV-2 have focused on responses to full-length spike protein, specific domains within spike, or nucleoprotein. In this study, we used high-density peptide microarrays representing the complete proteome of SARS-CoV-2 to identify binding sites (epitopes) targeted by antibodies present in the blood of COVID-19 resolved cases at 5 months post-diagnosis. Compared to previous studies that evaluated epitope-specific responses early post-diagnosis (< 60 days), we found that epitope-specific responses to nucleoprotein and spike protein have contracted, and that responses to membrane protein have expanded. Although antibody titers to full-length spike and nucleoprotein remain steady over months, taken together our data suggest that the population of epitope-specific antibodies that contribute to this reactivity is dynamic and evolves over time. Further, the spike epitopes bound by polyclonal antibodies in COVID-19 convalescent serum samples aligned with known target sites that can neutralize viral activity suggesting that the maintenance of these antibodies might provide rapid serological immunity. Finally, the most dominant epitopes for membrane protein and spike showed high diagnostic accuracy providing novel biomarkers to refine blood-based antibody tests. This study provides new insights into the specific regions of SARS-CoV-2 targeted by serum antibodies long after infection.
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spelling doaj.art-546c634b415c4ea4946983ed0fffb7992022-12-22T03:22:25ZengNature PortfolioScientific Reports2045-23222022-05-0112111510.1038/s41598-022-12032-8High-resolution analysis of long-term serum antibodies in humans following convalescence of SARS-CoV-2 infectionAntonio Facciuolo0Erin Scruten1Sean Lipsit2Amanda Lang3Zoë Parker Cates4Jocelyne M. Lew5Darryl Falzarano6Volker Gerdts7Anthony J. Kusalik8Scott Napper9Vaccine and Infectious Disease Organization (VIDO), University of SaskatchewanVaccine and Infectious Disease Organization (VIDO), University of SaskatchewanVaccine and Infectious Disease Organization (VIDO), University of SaskatchewanRoy Romanow Provincial Laboratory, Saskatchewan Health AuthorityDepartment of Computer Science, University of SaskatchewanVaccine and Infectious Disease Organization (VIDO), University of SaskatchewanVaccine and Infectious Disease Organization (VIDO), University of SaskatchewanVaccine and Infectious Disease Organization (VIDO), University of SaskatchewanDepartment of Computer Science, University of SaskatchewanVaccine and Infectious Disease Organization (VIDO), University of SaskatchewanAbstract Long-term antibody responses to SARS-CoV-2 have focused on responses to full-length spike protein, specific domains within spike, or nucleoprotein. In this study, we used high-density peptide microarrays representing the complete proteome of SARS-CoV-2 to identify binding sites (epitopes) targeted by antibodies present in the blood of COVID-19 resolved cases at 5 months post-diagnosis. Compared to previous studies that evaluated epitope-specific responses early post-diagnosis (< 60 days), we found that epitope-specific responses to nucleoprotein and spike protein have contracted, and that responses to membrane protein have expanded. Although antibody titers to full-length spike and nucleoprotein remain steady over months, taken together our data suggest that the population of epitope-specific antibodies that contribute to this reactivity is dynamic and evolves over time. Further, the spike epitopes bound by polyclonal antibodies in COVID-19 convalescent serum samples aligned with known target sites that can neutralize viral activity suggesting that the maintenance of these antibodies might provide rapid serological immunity. Finally, the most dominant epitopes for membrane protein and spike showed high diagnostic accuracy providing novel biomarkers to refine blood-based antibody tests. This study provides new insights into the specific regions of SARS-CoV-2 targeted by serum antibodies long after infection.https://doi.org/10.1038/s41598-022-12032-8
spellingShingle Antonio Facciuolo
Erin Scruten
Sean Lipsit
Amanda Lang
Zoë Parker Cates
Jocelyne M. Lew
Darryl Falzarano
Volker Gerdts
Anthony J. Kusalik
Scott Napper
High-resolution analysis of long-term serum antibodies in humans following convalescence of SARS-CoV-2 infection
Scientific Reports
title High-resolution analysis of long-term serum antibodies in humans following convalescence of SARS-CoV-2 infection
title_full High-resolution analysis of long-term serum antibodies in humans following convalescence of SARS-CoV-2 infection
title_fullStr High-resolution analysis of long-term serum antibodies in humans following convalescence of SARS-CoV-2 infection
title_full_unstemmed High-resolution analysis of long-term serum antibodies in humans following convalescence of SARS-CoV-2 infection
title_short High-resolution analysis of long-term serum antibodies in humans following convalescence of SARS-CoV-2 infection
title_sort high resolution analysis of long term serum antibodies in humans following convalescence of sars cov 2 infection
url https://doi.org/10.1038/s41598-022-12032-8
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