Glycan reactive anti-HIV-1 antibodies bind the SARS-CoV-2 spike protein but do not block viral entry

Abstract The SARS-CoV-2 spike glycoprotein is a focal point for vaccine immunogen and therapeutic antibody design, and also serves as a critical antigen in the evaluation of immune responses to COVID-19. A common feature amongst enveloped viruses such as SARS-CoV-2 and HIV-1 is the propensity for di...

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Main Authors: Dhiraj Mannar, Karoline Leopold, Sriram Subramaniam
Format: Article
Language:English
Published: Nature Portfolio 2021-06-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-91746-7
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author Dhiraj Mannar
Karoline Leopold
Sriram Subramaniam
author_facet Dhiraj Mannar
Karoline Leopold
Sriram Subramaniam
author_sort Dhiraj Mannar
collection DOAJ
description Abstract The SARS-CoV-2 spike glycoprotein is a focal point for vaccine immunogen and therapeutic antibody design, and also serves as a critical antigen in the evaluation of immune responses to COVID-19. A common feature amongst enveloped viruses such as SARS-CoV-2 and HIV-1 is the propensity for displaying host-derived glycans on entry spike proteins. Similarly displayed glycosylation motifs can serve as the basis for glyco-epitope mediated cross-reactivity by antibodies, which can have important implications on virus neutralization, antibody-dependent enhancement (ADE) of infection, and the interpretation of antibody titers in serological assays. From a panel of nine anti-HIV-1 gp120 reactive antibodies, we selected two (PGT126 and PGT128) that displayed high levels of cross-reactivity with the SARS-CoV-2 spike. We report that these antibodies are incapable of neutralizing pseudoviruses expressing SARS-CoV-2 spike proteins and are unlikely to mediate ADE via FcγRII receptor engagement. Nevertheless, ELISA and other immunoreactivity experiments demonstrate these antibodies are capable of binding the SARS-CoV-2 spike in a glycan-dependent manner. These results contribute to the growing literature surrounding SARS-CoV-2 S cross-reactivity, as we demonstrate the ability for cross-reactive antibodies to interfere in immunoassays.
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spelling doaj.art-c9bfdfbd0f564221a1e14578af51be7c2022-12-21T19:32:54ZengNature PortfolioScientific Reports2045-23222021-06-011111910.1038/s41598-021-91746-7Glycan reactive anti-HIV-1 antibodies bind the SARS-CoV-2 spike protein but do not block viral entryDhiraj Mannar0Karoline Leopold1Sriram Subramaniam2Department of Biochemistry and Molecular Biology, University of British ColumbiaDepartment of Biochemistry and Molecular Biology, University of British ColumbiaDepartment of Biochemistry and Molecular Biology, University of British ColumbiaAbstract The SARS-CoV-2 spike glycoprotein is a focal point for vaccine immunogen and therapeutic antibody design, and also serves as a critical antigen in the evaluation of immune responses to COVID-19. A common feature amongst enveloped viruses such as SARS-CoV-2 and HIV-1 is the propensity for displaying host-derived glycans on entry spike proteins. Similarly displayed glycosylation motifs can serve as the basis for glyco-epitope mediated cross-reactivity by antibodies, which can have important implications on virus neutralization, antibody-dependent enhancement (ADE) of infection, and the interpretation of antibody titers in serological assays. From a panel of nine anti-HIV-1 gp120 reactive antibodies, we selected two (PGT126 and PGT128) that displayed high levels of cross-reactivity with the SARS-CoV-2 spike. We report that these antibodies are incapable of neutralizing pseudoviruses expressing SARS-CoV-2 spike proteins and are unlikely to mediate ADE via FcγRII receptor engagement. Nevertheless, ELISA and other immunoreactivity experiments demonstrate these antibodies are capable of binding the SARS-CoV-2 spike in a glycan-dependent manner. These results contribute to the growing literature surrounding SARS-CoV-2 S cross-reactivity, as we demonstrate the ability for cross-reactive antibodies to interfere in immunoassays.https://doi.org/10.1038/s41598-021-91746-7
spellingShingle Dhiraj Mannar
Karoline Leopold
Sriram Subramaniam
Glycan reactive anti-HIV-1 antibodies bind the SARS-CoV-2 spike protein but do not block viral entry
Scientific Reports
title Glycan reactive anti-HIV-1 antibodies bind the SARS-CoV-2 spike protein but do not block viral entry
title_full Glycan reactive anti-HIV-1 antibodies bind the SARS-CoV-2 spike protein but do not block viral entry
title_fullStr Glycan reactive anti-HIV-1 antibodies bind the SARS-CoV-2 spike protein but do not block viral entry
title_full_unstemmed Glycan reactive anti-HIV-1 antibodies bind the SARS-CoV-2 spike protein but do not block viral entry
title_short Glycan reactive anti-HIV-1 antibodies bind the SARS-CoV-2 spike protein but do not block viral entry
title_sort glycan reactive anti hiv 1 antibodies bind the sars cov 2 spike protein but do not block viral entry
url https://doi.org/10.1038/s41598-021-91746-7
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AT karolineleopold glycanreactiveantihiv1antibodiesbindthesarscov2spikeproteinbutdonotblockviralentry
AT sriramsubramaniam glycanreactiveantihiv1antibodiesbindthesarscov2spikeproteinbutdonotblockviralentry