Glycan Masking of Epitopes in the NTD and RBD of the Spike Protein Elicits Broadly Neutralizing Antibodies Against SARS-CoV-2 Variants

Glycan-masking the vaccine antigen by mutating the undesired antigenic sites with an additional N-linked glycosylation motif can refocus B-cell responses to desired epitopes, without affecting the antigen’s overall-folded structure. This study examined the impact of glycan-masking mutants of the N-t...

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Autores principales:	Wei-Shuo Lin, I-Chen Chen, Hui-Chen Chen, Yi-Chien Lee, Suh-Chin Wu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	SARS-CoV-2 variant glycan masking COVID-19 vaccine Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/ace61be5a19e4c07b8f66dd0a2f31f07
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spelling	oai:doaj.org-article:ace61be5a19e4c07b8f66dd0a2f31f072021-12-02T09:48:56ZGlycan Masking of Epitopes in the NTD and RBD of the Spike Protein Elicits Broadly Neutralizing Antibodies Against SARS-CoV-2 Variants1664-322410.3389/fimmu.2021.795741https://doaj.org/article/ace61be5a19e4c07b8f66dd0a2f31f072021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.795741/fullhttps://doaj.org/toc/1664-3224Glycan-masking the vaccine antigen by mutating the undesired antigenic sites with an additional N-linked glycosylation motif can refocus B-cell responses to desired epitopes, without affecting the antigen’s overall-folded structure. This study examined the impact of glycan-masking mutants of the N-terminal domain (NTD) and receptor-binding domain (RBD) of SARS-CoV-2, and found that the antigenic design of the S protein increases the neutralizing antibody titers against the Wuhan-Hu-1 ancestral strain and the recently emerged SARS-CoV-2 variants Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2). Our results demonstrated that the use of glycan-masking Ad-S-R158N/Y160T in the NTD elicited a 2.8-fold, 6.5-fold, and 4.6-fold increase in the IC-50 NT titer against the Alpha (B.1.1.7), Beta (B.1.351) and Delta (B.1.617.2) variants, respectively. Glycan-masking of Ad-S-D428N in the RBD resulted in a 3.0-fold and 2.0-fold increase in the IC-50 neutralization titer against the Alpha (B.1.1.7) and Beta (B.1.351) variants, respectively. The use of glycan-masking in Ad-S-R158N/Y160T and Ad-S-D428N antigen design may help develop universal COVID-19 vaccines against current and future emerging SARS-CoV-2 variants.Wei-Shuo LinI-Chen ChenHui-Chen ChenYi-Chien LeeSuh-Chin WuSuh-Chin WuFrontiers Media S.A.articleSARS-CoV-2variantglycan maskingCOVID-19vaccineImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	SARS-CoV-2 variant glycan masking COVID-19 vaccine Immunologic diseases. Allergy RC581-607
spellingShingle	SARS-CoV-2 variant glycan masking COVID-19 vaccine Immunologic diseases. Allergy RC581-607 Wei-Shuo Lin I-Chen Chen Hui-Chen Chen Yi-Chien Lee Suh-Chin Wu Suh-Chin Wu Glycan Masking of Epitopes in the NTD and RBD of the Spike Protein Elicits Broadly Neutralizing Antibodies Against SARS-CoV-2 Variants
description	Glycan-masking the vaccine antigen by mutating the undesired antigenic sites with an additional N-linked glycosylation motif can refocus B-cell responses to desired epitopes, without affecting the antigen’s overall-folded structure. This study examined the impact of glycan-masking mutants of the N-terminal domain (NTD) and receptor-binding domain (RBD) of SARS-CoV-2, and found that the antigenic design of the S protein increases the neutralizing antibody titers against the Wuhan-Hu-1 ancestral strain and the recently emerged SARS-CoV-2 variants Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2). Our results demonstrated that the use of glycan-masking Ad-S-R158N/Y160T in the NTD elicited a 2.8-fold, 6.5-fold, and 4.6-fold increase in the IC-50 NT titer against the Alpha (B.1.1.7), Beta (B.1.351) and Delta (B.1.617.2) variants, respectively. Glycan-masking of Ad-S-D428N in the RBD resulted in a 3.0-fold and 2.0-fold increase in the IC-50 neutralization titer against the Alpha (B.1.1.7) and Beta (B.1.351) variants, respectively. The use of glycan-masking in Ad-S-R158N/Y160T and Ad-S-D428N antigen design may help develop universal COVID-19 vaccines against current and future emerging SARS-CoV-2 variants.
format	article
author	Wei-Shuo Lin I-Chen Chen Hui-Chen Chen Yi-Chien Lee Suh-Chin Wu Suh-Chin Wu
author_facet	Wei-Shuo Lin I-Chen Chen Hui-Chen Chen Yi-Chien Lee Suh-Chin Wu Suh-Chin Wu
author_sort	Wei-Shuo Lin
title	Glycan Masking of Epitopes in the NTD and RBD of the Spike Protein Elicits Broadly Neutralizing Antibodies Against SARS-CoV-2 Variants
title_short	Glycan Masking of Epitopes in the NTD and RBD of the Spike Protein Elicits Broadly Neutralizing Antibodies Against SARS-CoV-2 Variants
title_full	Glycan Masking of Epitopes in the NTD and RBD of the Spike Protein Elicits Broadly Neutralizing Antibodies Against SARS-CoV-2 Variants
title_fullStr	Glycan Masking of Epitopes in the NTD and RBD of the Spike Protein Elicits Broadly Neutralizing Antibodies Against SARS-CoV-2 Variants
title_full_unstemmed	Glycan Masking of Epitopes in the NTD and RBD of the Spike Protein Elicits Broadly Neutralizing Antibodies Against SARS-CoV-2 Variants
title_sort	glycan masking of epitopes in the ntd and rbd of the spike protein elicits broadly neutralizing antibodies against sars-cov-2 variants
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/ace61be5a19e4c07b8f66dd0a2f31f07
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Glycan Masking of Epitopes in the NTD and RBD of the Spike Protein Elicits Broadly Neutralizing Antibodies Against SARS-CoV-2 Variants

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