Year: 2023
Type: article
Abstract: Enveloped viruses co-opt host glycosylation pathways to decorate their surface proteins. As viruses evolve, emerging strains can modify their glycosylation patterns to influence host interactions and subvert immune recognition. Still, changes in viral glycosylation or their impact on antibody protection cannot be predicted from genomic sequences alone. Using the highly glycosylated SARS-CoV-2 Spike protein as a model system, we present a lectin fingerprinting method that rapidly reports on changes in variant glycosylation state, which are linked to antibody neutralization. In the presence of antibodies or convalescent and vaccinated patient sera, unique lectin fingerprints emerge that distinguish neutralizing versus non-neutralizing antibodies. This information could not be inferred from direct binding interactions between antibodies and the Spike receptor-binding domain (RBD) binding data alone. Comparative glycoproteomics of the Spike RBD of wild-type (Wuhan-Hu-1) and Delta (B.1.617.2) variants reveal O-glycosylation differences as a key determinant of immune recognition differences. These data underscore the interplay between viral glycosylation and immune recognition and reveal lectin fingerprinting to be a rapid, sensitive, and high-throughput assay to distinguish the neutralization potential of antibodies that target critical viral glycoproteins.
Source: ACS Central Science
Institutions: Massachusetts Institute of Technology, Ragon Institute of MGH, MIT and Harvard, Broad Institute, Harvard University, Massachusetts General Hospital, Center for Computational and Integrative Biology, Massachusetts General Hospital, University of Georgia, Koch Institute for Integrative Cancer Research At MIT
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
Awards: Demystifying the antiviral activity of the IgG3+ antibody response, G1330203626, G1491648497, G1813434710, G1910030611, G220646820, Synthetic Ligands for Directing Immune Responses, G3353571719, MIP: GlycoMIP - Automating the Synthesis of Rationally Designed Glycomaterials, G3607645992, G3636384462, G3702685841, G3891730054, G448405612, Epitope focusing using structure-based immunogen design approaches, G561983004, A National Glycoscience Resource - CCRC Service and Training, G6042108000, G6321917404, G707340384, G7183466680, G8137250695, G8275439092, G8632199966, G9000005946, G9000007979, G9000030784, G9000035625, G9000061568, G9000110780, G9000144868, G9000155537, G9000283030, G9000314418, Center for Viral Systems Biology (CViSB), G913457347, G933837111
OpenAlex ID: W4376105271