Relative Ratios of Human Seasonal Coronavirus Antibodies Predict the Efficiency of Cross-Neutralization of SARS-CoV-2 Spike Binding to ACE2

Background: Antibodies raised against human seasonal coronaviruses (sCoVs), which are responsible for the common cold, are known to cross-react with SARS-CoV-2 antigens. This prompts questions about their protective role against SARS-CoV-2 infections and COVID-19 severity. However, the relationship...

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Autores principales: Yannick Galipeau, Vinayakumar Siragam, Geneviève Laroche, Erika Marion, Matthew Greig, Michaeline McGuinty, Ronald A Booth, Yves Durocher, Miroslava Cuperlovic-Culf, Steffany A.L. Bennett, Angela M. Crawley, Patrick M. Giguère, Curtis Cooper, Marc-André Langlois
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Publicado: Elsevier 2021
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spelling oai:doaj.org-article:7ba81d4ec8dc43269394d064eb78b2d72021-12-02T05:01:54ZRelative Ratios of Human Seasonal Coronavirus Antibodies Predict the Efficiency of Cross-Neutralization of SARS-CoV-2 Spike Binding to ACE22352-396410.1016/j.ebiom.2021.103700https://doaj.org/article/7ba81d4ec8dc43269394d064eb78b2d72021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2352396421004941https://doaj.org/toc/2352-3964Background: Antibodies raised against human seasonal coronaviruses (sCoVs), which are responsible for the common cold, are known to cross-react with SARS-CoV-2 antigens. This prompts questions about their protective role against SARS-CoV-2 infections and COVID-19 severity. However, the relationship between sCoVs exposure and SARS-CoV-2 correlates of protection are not clearly identified. Methods: We performed a cross-sectional analysis of cross-reactivity and cross-neutralization to SARS-CoV-2 antigens (S-RBD, S-trimer, N) using pre-pandemic sera from four different groups: pediatrics and adolescents, individuals 21 to 70 years of age, older than 70 years of age, and individuals living with HCV or HIV. Data was then further analysed using machine learning to identify predictive patterns of neutralization based on sCoVs serology. Findings: Antibody cross-reactivity to SARS-CoV-2 antigens varied between 1.6% and 15.3% depending on the cohort and the isotype-antigen pair analyzed. We also show a range of neutralizing activity (0-45%) with median inhibition ranging from 17.6 % to 23.3 % in serum that interferes with SARS-CoV-2 spike attachment to ACE2 independently of age group. While the abundance of sCoV antibodies did not directly correlate with neutralization, we show that neutralizing activity is rather dependent on relative ratios of IgGs in sera directed to all four sCoV spike proteins. More specifically, we identified antibodies to NL63 and OC43 as being the most important predictors of neutralization. Interpretation: Our data support the concept that exposure to sCoVs triggers antibody responses that influence the efficiency of SARS-CoV-2 spike binding to ACE2, which may potentially impact COVID-19 disease severity through other latent variables. Funding: This study was supported by a grant by the CIHR (VR2 -172722) and by a grant supplement by the CITF, and by a NRC Collaborative R&D Initiative Grant (PR031-1).Yannick GalipeauVinayakumar SiragamGeneviève LarocheErika MarionMatthew GreigMichaeline McGuintyRonald A BoothYves DurocherMiroslava Cuperlovic-CulfSteffany A.L. BennettAngela M. CrawleyPatrick M. GiguèreCurtis CooperMarc-André LangloisElsevierarticleSARS-CoV-2COVID-19OC43NL63seasonal coronavirushuman coronavirusesMedicineRMedicine (General)R5-920ENEBioMedicine, Vol 74, Iss , Pp 103700- (2021)
institution DOAJ
collection DOAJ
language EN
topic SARS-CoV-2
COVID-19
OC43
NL63
seasonal coronavirus
human coronaviruses
Medicine
R
Medicine (General)
R5-920
spellingShingle SARS-CoV-2
COVID-19
OC43
NL63
seasonal coronavirus
human coronaviruses
Medicine
R
Medicine (General)
R5-920
Yannick Galipeau
Vinayakumar Siragam
Geneviève Laroche
Erika Marion
Matthew Greig
Michaeline McGuinty
Ronald A Booth
Yves Durocher
Miroslava Cuperlovic-Culf
Steffany A.L. Bennett
Angela M. Crawley
Patrick M. Giguère
Curtis Cooper
Marc-André Langlois
Relative Ratios of Human Seasonal Coronavirus Antibodies Predict the Efficiency of Cross-Neutralization of SARS-CoV-2 Spike Binding to ACE2
description Background: Antibodies raised against human seasonal coronaviruses (sCoVs), which are responsible for the common cold, are known to cross-react with SARS-CoV-2 antigens. This prompts questions about their protective role against SARS-CoV-2 infections and COVID-19 severity. However, the relationship between sCoVs exposure and SARS-CoV-2 correlates of protection are not clearly identified. Methods: We performed a cross-sectional analysis of cross-reactivity and cross-neutralization to SARS-CoV-2 antigens (S-RBD, S-trimer, N) using pre-pandemic sera from four different groups: pediatrics and adolescents, individuals 21 to 70 years of age, older than 70 years of age, and individuals living with HCV or HIV. Data was then further analysed using machine learning to identify predictive patterns of neutralization based on sCoVs serology. Findings: Antibody cross-reactivity to SARS-CoV-2 antigens varied between 1.6% and 15.3% depending on the cohort and the isotype-antigen pair analyzed. We also show a range of neutralizing activity (0-45%) with median inhibition ranging from 17.6 % to 23.3 % in serum that interferes with SARS-CoV-2 spike attachment to ACE2 independently of age group. While the abundance of sCoV antibodies did not directly correlate with neutralization, we show that neutralizing activity is rather dependent on relative ratios of IgGs in sera directed to all four sCoV spike proteins. More specifically, we identified antibodies to NL63 and OC43 as being the most important predictors of neutralization. Interpretation: Our data support the concept that exposure to sCoVs triggers antibody responses that influence the efficiency of SARS-CoV-2 spike binding to ACE2, which may potentially impact COVID-19 disease severity through other latent variables. Funding: This study was supported by a grant by the CIHR (VR2 -172722) and by a grant supplement by the CITF, and by a NRC Collaborative R&D Initiative Grant (PR031-1).
format article
author Yannick Galipeau
Vinayakumar Siragam
Geneviève Laroche
Erika Marion
Matthew Greig
Michaeline McGuinty
Ronald A Booth
Yves Durocher
Miroslava Cuperlovic-Culf
Steffany A.L. Bennett
Angela M. Crawley
Patrick M. Giguère
Curtis Cooper
Marc-André Langlois
author_facet Yannick Galipeau
Vinayakumar Siragam
Geneviève Laroche
Erika Marion
Matthew Greig
Michaeline McGuinty
Ronald A Booth
Yves Durocher
Miroslava Cuperlovic-Culf
Steffany A.L. Bennett
Angela M. Crawley
Patrick M. Giguère
Curtis Cooper
Marc-André Langlois
author_sort Yannick Galipeau
title Relative Ratios of Human Seasonal Coronavirus Antibodies Predict the Efficiency of Cross-Neutralization of SARS-CoV-2 Spike Binding to ACE2
title_short Relative Ratios of Human Seasonal Coronavirus Antibodies Predict the Efficiency of Cross-Neutralization of SARS-CoV-2 Spike Binding to ACE2
title_full Relative Ratios of Human Seasonal Coronavirus Antibodies Predict the Efficiency of Cross-Neutralization of SARS-CoV-2 Spike Binding to ACE2
title_fullStr Relative Ratios of Human Seasonal Coronavirus Antibodies Predict the Efficiency of Cross-Neutralization of SARS-CoV-2 Spike Binding to ACE2
title_full_unstemmed Relative Ratios of Human Seasonal Coronavirus Antibodies Predict the Efficiency of Cross-Neutralization of SARS-CoV-2 Spike Binding to ACE2
title_sort relative ratios of human seasonal coronavirus antibodies predict the efficiency of cross-neutralization of sars-cov-2 spike binding to ace2
publisher Elsevier
publishDate 2021
url https://doaj.org/article/7ba81d4ec8dc43269394d064eb78b2d7
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