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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 #MMPMID34925381
  • Lin WS; Chen IC; Chen HC; Lee YC; Wu SC
  • Front Immunol 2021[]; 12 (ä): 795741 PMID34925381show ga
  • 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.
  • |Adenoviridae/genetics[MESH]
  • |Animals[MESH]
  • |Antibodies, Neutralizing/immunology[MESH]
  • |Antibodies, Viral/immunology[MESH]
  • |Antibody Formation/immunology[MESH]
  • |Antigens, Viral/*immunology[MESH]
  • |COVID-19 Vaccines/genetics/immunology[MESH]
  • |COVID-19/*immunology/prevention & control/virology[MESH]
  • |Disease Models, Animal[MESH]
  • |Dose-Response Relationship, Immunologic[MESH]
  • |Epitopes/*immunology[MESH]
  • |Female[MESH]
  • |Genetic Engineering[MESH]
  • |Genetic Vectors/genetics[MESH]
  • |Humans[MESH]
  • |Immunization[MESH]
  • |Mice[MESH]
  • |Neutralization Tests[MESH]
  • |Polysaccharides[MESH]
  • |Protein Interaction Domains and Motifs/*immunology[MESH]
  • |SARS-CoV-2/genetics/*immunology[MESH]
  • |Spike Glycoprotein, Coronavirus/chemistry/genetics/*immunology/metabolism[MESH]
  • |Structure-Activity Relationship[MESH]

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  • suck abstract from ncbi

    795741 ä.12 2021