Lectin Fingerprinting Distinguishes Antibody Neutralization in SARS-CoV‑2
Authors:
Michael G. Wuo, Amanda E. Dugan, Melanie Halim, Blake M. Hauser, Jared Feldman, Timothy M. Caradonna, Shuting Zhang, Lauren E. Pepi, Caroline Atyeo, Stephanie Fischinger, Galit Alter, Wilfredo F. Garcia-Beltran, Parastoo Azadi, Deb Hung, Aaron G. Schmidt, and Laura L. Kiessling*
Affiliation:
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts 02139, United States
The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, United States
Department of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, Massachusetts 02139, United States
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, United States
Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602, United States
Department of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, Massachusetts 02139, United States
Description:
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.
Publications:
- Wuo, Michael G., et al.; Lectin Fingerprinting Distinguishes Antibody Neutralization in SARS-CoV-2; ACS Central Science, 2023
Tags:
Biopolymers Carbohydrates Chemical biology Immunology SARS-CoV-2Files:
No related files available