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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.
Front Immunol. 2021; 12:795741.FI

Abstract

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.

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Authors+Show Affiliations

Lin WS
Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan.
Chen IC
Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan.
Chen HC
Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan.
Lee YC
Department of Infectious Diseases, Fu Jen Catholic University Hospital, New Taipei City, Taiwan.
Wu SC
Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan. Department of Medical Science, National Tsing Hua University, Hsinchu, Taiwan.

MeSH

AdenoviridaeAnimalsAntibodies, NeutralizingAntibodies, ViralAntibody FormationAntigens, ViralCOVID-19COVID-19 VaccinesDisease Models, AnimalDose-Response Relationship, ImmunologicEpitopesFemaleGenetic EngineeringGenetic VectorsHumansImmunizationMiceNeutralization TestsPolysaccharidesProtein Interaction Domains and MotifsSARS-CoV-2Spike Glycoprotein, CoronavirusStructure-Activity Relationship

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34925381

Citation

Lin, Wei-Shuo, et al. "Glycan Masking of Epitopes in the NTD and RBD of the Spike Protein Elicits Broadly Neutralizing Antibodies Against SARS-CoV-2 Variants." Frontiers in Immunology, vol. 12, 2021, p. 795741.
Lin WS, Chen IC, Chen HC, et al. Glycan Masking of Epitopes in the NTD and RBD of the Spike Protein Elicits Broadly Neutralizing Antibodies Against SARS-CoV-2 Variants. Front Immunol. 2021;12:795741.
Lin, W. S., Chen, I. C., Chen, H. C., Lee, Y. C., & Wu, S. C. (2021). Glycan Masking of Epitopes in the NTD and RBD of the Spike Protein Elicits Broadly Neutralizing Antibodies Against SARS-CoV-2 Variants. Frontiers in Immunology, 12, 795741. https://doi.org/10.3389/fimmu.2021.795741
Lin WS, et al. Glycan Masking of Epitopes in the NTD and RBD of the Spike Protein Elicits Broadly Neutralizing Antibodies Against SARS-CoV-2 Variants. Front Immunol. 2021;12:795741. PubMed PMID: 34925381.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Glycan Masking of Epitopes in the NTD and RBD of the Spike Protein Elicits Broadly Neutralizing Antibodies Against SARS-CoV-2 Variants. AU - Lin,Wei-Shuo, AU - Chen,I-Chen, AU - Chen,Hui-Chen, AU - Lee,Yi-Chien, AU - Wu,Suh-Chin, Y1 - 2021/12/02/ PY - 2021/10/15/received PY - 2021/11/17/accepted PY - 2021/12/20/entrez PY - 2021/12/21/pubmed PY - 2022/1/5/medline KW - COVID-19 KW - SARS-CoV-2 KW - glycan masking KW - vaccine KW - variant SP - 795741 EP - 795741 JF - Frontiers in immunology JO - Front Immunol VL - 12 N2 - 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. SN - 1664-3224 UR - https://www.unboundmedicine.com/medline/citation/34925381/Glycan_Masking_of_Epitopes_in_the_NTD_and_RBD_of_the_Spike_Protein_Elicits_Broadly_Neutralizing_Antibodies_Against_SARS_CoV_2_Variants_ DB - PRIME DP - Unbound Medicine ER -