Glycomic Analysis Identifies Pre-Vaccination Markers of Response to Influenza Vaccine, Implicating the Complement Pathway

Abstract

ABSTRACTResponse to vaccination can vary significantly from person to person. A key to improving vaccine design and vaccination strategy is to understand the mechanism behind this variation. The role of glycosylation, a critical modulator of immunity, is unknown in determining vaccine responses. To gain insight into the association between glycosylation and vaccine-induced antibody levels we profiled the pre- and post-vaccination serum protein glycomes of 160 Caucasian adults receiving the FLUZONE™ influenza vaccine during the 2019-2020 influenza season. Using lectin microarrays, we observed that pre-vaccination levels of Lewis A antigen (Lea) are significantly higher in people who did not mount significant antibody responses, when compared to 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. We also observed post-vaccination increases in sialyl Lewis X antigen (sLex) and decreases in high mannose glycans among high responders, which were not observed in non-responders. This data suggests that the immune system may actively modulate glycosylation as part of its effort to establish effective protection post-vaccination.