Differential patterns of cross-reactive antibody response against SARS-CoV-2 spike protein detected for chronically ill and healthy COVID-19 naïve individuals

Abstract Immunity to previously encountered viruses can alter response to unrelated pathogens. We reasoned that similar mechanism may also involve SARS-CoV-2 and thereby affect the specificity and the quality of the immune response against the virus. Here, we employed high-throughput next generation...

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Main Authors: Mariliis Jaago, Annika Rähni, Nadežda Pupina, Arno Pihlak, Helle Sadam, Jürgen Tuvikene, Annela Avarlaid, Anu Planken, Margus Planken, Liina Haring, Eero Vasar, Miljana Baćević, France Lambert, Eija Kalso, Pirkko Pussinen, Pentti J. Tienari, Antti Vaheri, Dan Lindholm, Tõnis Timmusk, Amir M. Ghaemmaghami, Kaia Palm
Format: Article
Language:English
Published: Nature Portfolio 2022-10-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-20849-6
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author Mariliis Jaago
Annika Rähni
Nadežda Pupina
Arno Pihlak
Helle Sadam
Jürgen Tuvikene
Annela Avarlaid
Anu Planken
Margus Planken
Liina Haring
Eero Vasar
Miljana Baćević
France Lambert
Eija Kalso
Pirkko Pussinen
Pentti J. Tienari
Antti Vaheri
Dan Lindholm
Tõnis Timmusk
Amir M. Ghaemmaghami
Kaia Palm
author_facet Mariliis Jaago
Annika Rähni
Nadežda Pupina
Arno Pihlak
Helle Sadam
Jürgen Tuvikene
Annela Avarlaid
Anu Planken
Margus Planken
Liina Haring
Eero Vasar
Miljana Baćević
France Lambert
Eija Kalso
Pirkko Pussinen
Pentti J. Tienari
Antti Vaheri
Dan Lindholm
Tõnis Timmusk
Amir M. Ghaemmaghami
Kaia Palm
author_sort Mariliis Jaago
collection DOAJ
description Abstract Immunity to previously encountered viruses can alter response to unrelated pathogens. We reasoned that similar mechanism may also involve SARS-CoV-2 and thereby affect the specificity and the quality of the immune response against the virus. Here, we employed high-throughput next generation phage display method to explore the link between antibody immune response to previously encountered antigens and spike (S) glycoprotein. By profiling the antibody response in COVID-19 naïve individuals with a diverse clinical history (including cardiovascular, neurological, or oncological diseases), we identified 15 highly antigenic epitopes on spike protein that showed cross-reactivity with antigens of seasonal, persistent, latent or chronic infections from common human viruses. We observed varying degrees of cross-reactivity of different viral antigens with S in an epitope-specific manner. The data show that pre-existing SARS-CoV-2 S1 and S2 cross-reactive serum antibody is readily detectable in pre-pandemic cohort. In the severe COVID-19 cases, we found differential antibody response to the 15 defined antigenic and cross-reactive epitopes on spike. We also noted that despite the high mutation rates of Omicron (B.1.1.529) variants of SARS-CoV-2, some of the epitopes overlapped with the described mutations. Finally, we propose that the resolved epitopes on spike if targeted by re-called antibody response from SARS-CoV-2 infections or vaccinations can function in chronically ill COVID-19 naïve/unvaccinated individuals as immunogenic targets to boost antibodies augmenting the chronic conditions. Understanding the relationships between prior antigen exposure at the antibody epitope level and the immune response to subsequent infections with viruses from a different strain is paramount to guiding strategies to exit the COVID-19 pandemic.
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spelling doaj.art-616c68ebb3e24ae7b8bf2a3ef464fb1f2022-12-22T03:38:23ZengNature PortfolioScientific Reports2045-23222022-10-0112111910.1038/s41598-022-20849-6Differential patterns of cross-reactive antibody response against SARS-CoV-2 spike protein detected for chronically ill and healthy COVID-19 naïve individualsMariliis Jaago0Annika Rähni1Nadežda Pupina2Arno Pihlak3Helle Sadam4Jürgen Tuvikene5Annela Avarlaid6Anu Planken7Margus Planken8Liina Haring9Eero Vasar10Miljana Baćević11France Lambert12Eija Kalso13Pirkko Pussinen14Pentti J. Tienari15Antti Vaheri16Dan Lindholm17Tõnis Timmusk18Amir M. Ghaemmaghami19Kaia Palm20Protobios LLCProtobios LLCProtobios LLCProtobios LLCProtobios LLCProtobios LLCDepartment of Chemistry and Biotechnology, Tallinn University of TechnologyNorth Estonia Medical Centre FoundationNorth Estonia Medical Centre FoundationInstitute of Clinical Medicine, Psychiatry Clinic of Tartu University Hospital, University of TartuDepartment of Physiology, Institute of Biomedicine and Translational Medicine, University of TartuDental Biomaterial Research Unit (d-BRU), Faculty of Medicine, University of LiegeDepartment of Periodontology and Oral Surgery, Faculty of Medicine, University of LiegeDepartment of Anaesthesiology, Intensive Care and Pain Medicine, Helsinki University HospitalOral and Maxillofacial Diseases, Helsinki University Hospital, University of HelsinkiTranslational Immunology Research Program, Department of Neurology, Neurocenter, Helsinki University Hospital, University of HelsinkiDepartment of Virology, Medicum, University of HelsinkiDepartment of Biochemistry and Developmental Biology, Faculty of Medicine, University of HelsinkiProtobios LLCImmunology and Immuno-Bioengineering Group, School of Life Science, Faculty of Medicine and Health Sciences, University of NottinghamProtobios LLCAbstract Immunity to previously encountered viruses can alter response to unrelated pathogens. We reasoned that similar mechanism may also involve SARS-CoV-2 and thereby affect the specificity and the quality of the immune response against the virus. Here, we employed high-throughput next generation phage display method to explore the link between antibody immune response to previously encountered antigens and spike (S) glycoprotein. By profiling the antibody response in COVID-19 naïve individuals with a diverse clinical history (including cardiovascular, neurological, or oncological diseases), we identified 15 highly antigenic epitopes on spike protein that showed cross-reactivity with antigens of seasonal, persistent, latent or chronic infections from common human viruses. We observed varying degrees of cross-reactivity of different viral antigens with S in an epitope-specific manner. The data show that pre-existing SARS-CoV-2 S1 and S2 cross-reactive serum antibody is readily detectable in pre-pandemic cohort. In the severe COVID-19 cases, we found differential antibody response to the 15 defined antigenic and cross-reactive epitopes on spike. We also noted that despite the high mutation rates of Omicron (B.1.1.529) variants of SARS-CoV-2, some of the epitopes overlapped with the described mutations. Finally, we propose that the resolved epitopes on spike if targeted by re-called antibody response from SARS-CoV-2 infections or vaccinations can function in chronically ill COVID-19 naïve/unvaccinated individuals as immunogenic targets to boost antibodies augmenting the chronic conditions. Understanding the relationships between prior antigen exposure at the antibody epitope level and the immune response to subsequent infections with viruses from a different strain is paramount to guiding strategies to exit the COVID-19 pandemic.https://doi.org/10.1038/s41598-022-20849-6
spellingShingle Mariliis Jaago
Annika Rähni
Nadežda Pupina
Arno Pihlak
Helle Sadam
Jürgen Tuvikene
Annela Avarlaid
Anu Planken
Margus Planken
Liina Haring
Eero Vasar
Miljana Baćević
France Lambert
Eija Kalso
Pirkko Pussinen
Pentti J. Tienari
Antti Vaheri
Dan Lindholm
Tõnis Timmusk
Amir M. Ghaemmaghami
Kaia Palm
Differential patterns of cross-reactive antibody response against SARS-CoV-2 spike protein detected for chronically ill and healthy COVID-19 naïve individuals
Scientific Reports
title Differential patterns of cross-reactive antibody response against SARS-CoV-2 spike protein detected for chronically ill and healthy COVID-19 naïve individuals
title_full Differential patterns of cross-reactive antibody response against SARS-CoV-2 spike protein detected for chronically ill and healthy COVID-19 naïve individuals
title_fullStr Differential patterns of cross-reactive antibody response against SARS-CoV-2 spike protein detected for chronically ill and healthy COVID-19 naïve individuals
title_full_unstemmed Differential patterns of cross-reactive antibody response against SARS-CoV-2 spike protein detected for chronically ill and healthy COVID-19 naïve individuals
title_short Differential patterns of cross-reactive antibody response against SARS-CoV-2 spike protein detected for chronically ill and healthy COVID-19 naïve individuals
title_sort differential patterns of cross reactive antibody response against sars cov 2 spike protein detected for chronically ill and healthy covid 19 naive individuals
url https://doi.org/10.1038/s41598-022-20849-6
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