Correction: Antigen-Specific Antibody Glycosylation Is Regulated via Vaccination
Fig 1
Antibody glycosylation is programmed in an antigen-specific manner.
(A) Glycosylation was assessed on whole bulk-circulating and antigen-specific IgG antibodies directed against gp120 (n = 103), p24 (n = 47), and HA (n = 40) isolated from a cohort of 193 HIV-infected subjects. The dot plots represent the percent of glycan structures that contain galactose (G0 = agalactosylated, G1 = mono-galactosylated, G2 = di-galactosylated) or that contain sialic acid (S = sialylated), fucose (F = fucosylated), or a bisecting GlcNAc (B = bisected). Differences between groups were compared using Kruskal-Wallis test with Dunn’s multiple comparison’s test (*p<0.05, **p<0.01, ***p<0.001, ****p<0.0001). (B) Differences in glycosylation for gp120-specific antibodies from chronic treated (orange), chronic untreated (pink), viremic controller (purple) and elite controller (green) HIV patients were compared using two-way ANOVA with Tukey’s multiple comparison test (*p<0.05, **p<0.01, ***p<0.001, ****p<0.0001). (C) Antibody glycosylation levels on gp120-specific antibodies among chronic HIV-infected individuals were measured along with seven different gp120-specific effector functions. The correlations between gp120-specific antibody glycosylation and gp120-specific functional parameters were assessed using spearman correlations. Antibody dependent complement deposition (ADCD), antibody dependent cellular cytotoxicity (ADCC), antibody mediated NK cell activation (degranulation-CD107a, IFN-γ, or MIP-β secretion), antibody dependent cellular phagocytosis (ADCP), and antibody dependent cellular viral inhibition (ADCVI) are depicted. Significant correlations were identified for: Fucose—ADCC*, Di-sialylated—ADCC**, mono-galactosylated—ADCP*, Di-galactosylated—ADCP**, Bisection—ADCP* and Mono-sialylated—ADCP** (*p<0.05, **p<0.01, ***p<0.001, ****p<0.0001). (D), (E) To gain a multivariate sense of the overall glycan profile differences among antigen-specific antibodies, antigen-specific antibody glycan profiles (gp120- (teal), HA- (yellow) and p24- (red) specific antibodies) were compared using principle components analysis (PCA). Each dot on the score plot (D) represents an antigen-specific antibody glycan profile from a single individual and the loadings plot (E) shows the contribution of individual analyzed glycan structures to driving the separation between the antigen-specific antibody glycan profiles. Vector length represents the magnitude of individual glycan structure effects on overall separation in antibody glycan profiles, with longer vectors represent features that are further from the mean and that drive a larger effect on separating antibody glycan profiles. Moreover, location on the loadings plot is identical to location on the score plot, determined by the collective influence of all vectors. This analysis accounts for 42.9% of the glycosylation variation across the antigen-specific antibody specificities.