Functional Analysis of Human and Feline Coronavirus Cross-Reactive Antibodies Directed Against the SARS-CoV-2 Fusion Peptide

To face the continuous emergence of SARS-CoV-2 variants, broadly protective therapeutic antibodies are highly needed. We here focused on the fusion peptide (FP) region of the viral spike antigen since it is highly conserved among alpha- and betacoronaviruses. First, we found that coronavirus cross-r...

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Main Authors: Nathalie Vanderheijden, Annelies Stevaert, Jiexiong Xie, Xiaolei Ren, Cyril Barbezange, Sam Noppen, Isabelle Desombere, Bruno Verhasselt, Peter Geldhof, Nick Vereecke, Veerle Stroobants, Dayoung Oh, Merijn Vanhee, Lieve M. J. Naesens, Hans J. Nauwynck
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-01-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2021.790415/full
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author Nathalie Vanderheijden
Annelies Stevaert
Jiexiong Xie
Xiaolei Ren
Cyril Barbezange
Sam Noppen
Isabelle Desombere
Bruno Verhasselt
Peter Geldhof
Nick Vereecke
Nick Vereecke
Veerle Stroobants
Dayoung Oh
Merijn Vanhee
Lieve M. J. Naesens
Hans J. Nauwynck
author_facet Nathalie Vanderheijden
Annelies Stevaert
Jiexiong Xie
Xiaolei Ren
Cyril Barbezange
Sam Noppen
Isabelle Desombere
Bruno Verhasselt
Peter Geldhof
Nick Vereecke
Nick Vereecke
Veerle Stroobants
Dayoung Oh
Merijn Vanhee
Lieve M. J. Naesens
Hans J. Nauwynck
author_sort Nathalie Vanderheijden
collection DOAJ
description To face the continuous emergence of SARS-CoV-2 variants, broadly protective therapeutic antibodies are highly needed. We here focused on the fusion peptide (FP) region of the viral spike antigen since it is highly conserved among alpha- and betacoronaviruses. First, we found that coronavirus cross-reactive antibodies are commonly formed during infection, being omnipresent in sera from COVID-19 patients, in ~50% of pre-pandemic human sera (rich in antibodies against endemic human coronaviruses), and even in feline coronavirus-infected cats. Pepscan analyses demonstrated that a confined N-terminal region of the FP is strongly immunogenic across diverse coronaviruses. Peptide-purified human antibodies targeting this conserved FP epitope exhibited broad binding of alpha- and betacoronaviruses, besides weak and transient SARS-CoV-2 neutralizing activity. Being frequently elicited by coronavirus infection, these FP-binding antibodies might potentially exhibit Fc-mediated effector functions and influence the kinetics or severity of coronavirus infection and disease.
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spelling doaj.art-b6aa29b28bd34fa688c7003f07e0b0212022-12-22T04:04:11ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-01-011210.3389/fimmu.2021.790415790415Functional Analysis of Human and Feline Coronavirus Cross-Reactive Antibodies Directed Against the SARS-CoV-2 Fusion PeptideNathalie Vanderheijden0Annelies Stevaert1Jiexiong Xie2Xiaolei Ren3Cyril Barbezange4Sam Noppen5Isabelle Desombere6Bruno Verhasselt7Peter Geldhof8Nick Vereecke9Nick Vereecke10Veerle Stroobants11Dayoung Oh12Merijn Vanhee13Lieve M. J. Naesens14Hans J. Nauwynck15Laboratory of Virology, Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, Merelbeke, BelgiumRega Institute for Medical Research, Department of Microbiology, Immunology and Transplantation, KU Leuven – University of Leuven, Leuven, BelgiumLaboratory of Virology, Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, Merelbeke, BelgiumLaboratory of Virology, Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, Merelbeke, BelgiumNational Influenza Centre and Epidemiology of Infectious Diseases, Sciensano, Brussels, BelgiumRega Institute for Medical Research, Department of Microbiology, Immunology and Transplantation, KU Leuven – University of Leuven, Leuven, BelgiumImmune Response, Sciensano, Brussels, BelgiumLaboratory for Medical Microbiology, Ghent University Hospital, Ghent, BelgiumLaboratory of Parasitology, Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, Merelbeke, BelgiumLaboratory of Virology, Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, Merelbeke, BelgiumPathoSense BV, Lier, BelgiumLaboratory of Virology, Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, Merelbeke, BelgiumLaboratory of Virology, Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, Merelbeke, BelgiumDepartment of Laboratory Medicine, AZ Sint-Jan Brugge-Oostende, Bruges, BelgiumRega Institute for Medical Research, Department of Microbiology, Immunology and Transplantation, KU Leuven – University of Leuven, Leuven, BelgiumLaboratory of Virology, Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, Merelbeke, BelgiumTo face the continuous emergence of SARS-CoV-2 variants, broadly protective therapeutic antibodies are highly needed. We here focused on the fusion peptide (FP) region of the viral spike antigen since it is highly conserved among alpha- and betacoronaviruses. First, we found that coronavirus cross-reactive antibodies are commonly formed during infection, being omnipresent in sera from COVID-19 patients, in ~50% of pre-pandemic human sera (rich in antibodies against endemic human coronaviruses), and even in feline coronavirus-infected cats. Pepscan analyses demonstrated that a confined N-terminal region of the FP is strongly immunogenic across diverse coronaviruses. Peptide-purified human antibodies targeting this conserved FP epitope exhibited broad binding of alpha- and betacoronaviruses, besides weak and transient SARS-CoV-2 neutralizing activity. Being frequently elicited by coronavirus infection, these FP-binding antibodies might potentially exhibit Fc-mediated effector functions and influence the kinetics or severity of coronavirus infection and disease.https://www.frontiersin.org/articles/10.3389/fimmu.2021.790415/fullSARS-CoV-2fusion peptidespikeS2 subunitbroadly neutralizing antibodiescoronaviruses
spellingShingle Nathalie Vanderheijden
Annelies Stevaert
Jiexiong Xie
Xiaolei Ren
Cyril Barbezange
Sam Noppen
Isabelle Desombere
Bruno Verhasselt
Peter Geldhof
Nick Vereecke
Nick Vereecke
Veerle Stroobants
Dayoung Oh
Merijn Vanhee
Lieve M. J. Naesens
Hans J. Nauwynck
Functional Analysis of Human and Feline Coronavirus Cross-Reactive Antibodies Directed Against the SARS-CoV-2 Fusion Peptide
Frontiers in Immunology
SARS-CoV-2
fusion peptide
spike
S2 subunit
broadly neutralizing antibodies
coronaviruses
title Functional Analysis of Human and Feline Coronavirus Cross-Reactive Antibodies Directed Against the SARS-CoV-2 Fusion Peptide
title_full Functional Analysis of Human and Feline Coronavirus Cross-Reactive Antibodies Directed Against the SARS-CoV-2 Fusion Peptide
title_fullStr Functional Analysis of Human and Feline Coronavirus Cross-Reactive Antibodies Directed Against the SARS-CoV-2 Fusion Peptide
title_full_unstemmed Functional Analysis of Human and Feline Coronavirus Cross-Reactive Antibodies Directed Against the SARS-CoV-2 Fusion Peptide
title_short Functional Analysis of Human and Feline Coronavirus Cross-Reactive Antibodies Directed Against the SARS-CoV-2 Fusion Peptide
title_sort functional analysis of human and feline coronavirus cross reactive antibodies directed against the sars cov 2 fusion peptide
topic SARS-CoV-2
fusion peptide
spike
S2 subunit
broadly neutralizing antibodies
coronaviruses
url https://www.frontiersin.org/articles/10.3389/fimmu.2021.790415/full
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