Lectin Fingerprinting Distinguishes Antibody Neutralization in SARS-CoV-2
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lectin-fingerprinting-distinguishes-antibody-neutralization-in-sars-cov-2.pdf
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5.93 MB
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Author(s)
Wuo, Michael
Dugan, Amanda
Halim, Melanie
Hauser, Blake
Feldman, Jared
Caradonna, Timothy
Zhang, Shuting
Pepi, Lauren
Atyeo, Caroline
Fischinger, Stephanie
Date Issued
May 10, 2023
Journal
ACS Central Science
Publisher
American Chemical Society
Citation
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, Laura L. Kiessling; Lectin Fingerprinting Distinguishes Antibody Neutralization in SARS-CoV‑2. ACS Cent. Sci. 24 May 2023; 9 (5): 947–956.
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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Creative Commons Attribution
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DOI of Published Version
https://doi.org/10.1021/acscentsci.2c01471
