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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Autores principales:	Dhiraj Mannar, Karoline Leopold, Sriram Subramaniam
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c9bfdfbd0f564221a1e14578af51be7c
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spelling	oai:doaj.org-article:c9bfdfbd0f564221a1e14578af51be7c2021-12-02T17:23:26ZGlycan reactive anti-HIV-1 antibodies bind the SARS-CoV-2 spike protein but do not block viral entry10.1038/s41598-021-91746-72045-2322https://doaj.org/article/c9bfdfbd0f564221a1e14578af51be7c2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91746-7https://doaj.org/toc/2045-2322Abstract 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.Dhiraj MannarKaroline LeopoldSriram SubramaniamNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
author	Dhiraj Mannar Karoline Leopold Sriram Subramaniam
author_facet	Dhiraj Mannar Karoline Leopold Sriram Subramaniam
author_sort	Dhiraj Mannar
title	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_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_sort	glycan reactive anti-hiv-1 antibodies bind the sars-cov-2 spike protein but do not block viral entry
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c9bfdfbd0f564221a1e14578af51be7c
work_keys_str_mv	AT dhirajmannar glycanreactiveantihiv1antibodiesbindthesarscov2spikeproteinbutdonotblockviralentry AT karolineleopold glycanreactiveantihiv1antibodiesbindthesarscov2spikeproteinbutdonotblockviralentry AT sriramsubramaniam glycanreactiveantihiv1antibodiesbindthesarscov2spikeproteinbutdonotblockviralentry
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Glycan reactive anti-HIV-1 antibodies bind the SARS-CoV-2 spike protein but do not block viral entry

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