Prevaccination Glycan Markers of Response to an Influenza Vaccine Implicate the Complement Pathway

A key to improving
vaccine design and vaccination strategy is to
understand the mechanism behind the variation of vaccine response
with host factors. Glycosylation, a critical modulator of immunity,
has no clear role in determining vaccine responses. To gain insight
into the association between glycosylation and vaccine-induced antibody
levels, we profiled the pre- and postvaccination serum protein glycomes
of 160 Caucasian adults receiving the FLUZONE influenza vaccine during
the 2019–2020 influenza season using lectin microarray technology.
We found that prevaccination levels of Lewis A antigen (Lea) are significantly higher in nonresponders than responders. Glycoproteomic
analysis showed that Lea-bearing proteins are enriched
in complement activation pathways, suggesting a potential role of
glycosylation in tuning the activities of complement proteins, which
may be implicated in mounting vaccine responses. In addition, we observed
a postvaccination increase in sialyl Lewis X antigen (sLex) and a decrease in high mannose glycans among high responders, which
were not observed in nonresponders. These data suggest that the immune
system may actively modulate glycosylation as part of its effort to
establish effective protection postvaccination.