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.