Changes in Antigen-specific IgG1 Fc N-glycosylation Upon Influenza and Tetanus Vaccination

Abstract

Antibody effector functions have been shown to be influenced by the structure of the Fc N-glycans. Here we studied the changes in plasma or serum IgG Fc N-glycosylation upon vaccination of 10 Caucasian adults and 10 African children. Serum/plasma IgG was purified by affinity chromatography prior to and at two time points after vaccination. Fc N-glycosylation profiles of individual IgG subclasses were determined for both total IgG and affinity-purified anti-vaccine IgG using a recently developed fast nanoliquid chromatography-electrospray ionization MS (LC-ESI-MS) method. While vaccination had no effect on the glycosylation of total IgG, anti-vaccine IgG showed increased levels of galactosylation and sialylation upon active immunization. Interestingly, the number of sialic acids per galactose increased during the vaccination time course, suggesting a distinct regulation of galactosylation and sialylation. In addition we observed a decrease in the level of IgG1 bisecting N-acetylglucosamine whereas no significant changes were observed for the level of fucosylation. Our data indicate that dependent on the vaccination time point the infectious agent will encounter IgGs with different glycosylation profiles, which are expected to influence the antibody effector functions relevant in immunity.

Glycosylation pattern of anti‐platelet IgG is stable during pregnancy and predicts clinical outcome in alloimmune thrombocytopenia

“…Statistical analyses were performed using paired t-test (comparing glycosylation-levels in first and subsequent available pregnancies) and Kruskal Wallis test (comparing subsequent pregnancies after the index pregnancy). during pregnancy and decrease after delivery (van de Geijn et al, 2009) (and this study) and is transiently increased after immunization (Selman et al, 2012a;Vestrheim et al, 2014). Interestingly, we found that anti-HPA-1a IgG1-Fc galactosylation remained high after delivery, suggesting that the antigen-specific IgG1 galactosylation is less influenced by systemic changes induced by pregnancy.…”

“…For example, vaccination shows transient increases in IgG galactosylation and sialylation while fucosylation is stable and remains high (Selman et al, 2012a;Bakovic et al, 2013;Vestrheim et al, 2014). The level of galactosylated IgG changes with age, disease and pregnancy (Malhotra et al, 1995;Pucic et al, 2011;Bakovic et al, 2013).…”

Deconstructing the Antiviral Neutralizing-Antibody Response: Implications for Vaccine Development and Immunity

“…All IgG subclasses encode an N-linked glycosylation site at residue 297 of the heavy chain. While the position of the glycosylation site is conserved, the composition and structure of the oligosaccharide added to the antibody are influenced by the host immune activation state (134,135). Variation in the antibody glycoform provides a mechanism by which antibody effector function can be fine-tuned beyond class switch recombination.…”

Immunological responses to influenza vaccination: lessons for improving vaccine efficacy

“…This discovery was made through characterization of the natural anti-HA Fc domain repertoire after seasonal vaccination in adults. It was observed that baseline levels of anti-HA IgG Fc sialylation correlated with the quality of response (affinity and hemagglutination inhibition titer) to the seasonal influenza virus vaccine [20,48]. This finding suggested a feedback mechanism for regulation of B cell selection after vaccination by sialylated ICs.…”