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. 2023 Aug 14;26(9):107619.
doi: 10.1016/j.isci.2023.107619. eCollection 2023 Sep 15.

Comparative analysis of spike-specific IgG Fc glycoprofiles elicited by adenoviral, mRNA, and protein-based SARS-CoV-2 vaccines

Julie Van Coillie  1   2 , Tamas Pongracz  3 , Tonći Šuštić  1   2 , Wenjun Wang  3 , Jan Nouta  3 , Mathieu Le Gars  4 , Sofie Keijzer  5 , Federica Linty  1   2 , Olvi Cristianawati  5 , Jim B D Keijser  5 , Remco Visser  1   2 , Lonneke A van Vught  6   7 , Marleen A Slim  6   7 , Niels van Mourik  6   7 , Merel J Smit  8 , Adam Sander  9   10 , David E Schmidt  1 , Maurice Steenhuis  5 , Theo Rispens  5 , Morten A Nielsen  9 , Benjamin G Mordmüller  8 , Alexander P J Vlaar  7   11 , C Ellen van der Schoot  1 , Ramon Roozendaal  4 , Manfred Wuhrer  3 , Gestur Vidarsson  1   2 ; UMC COVID-19 S3/HCW study group; Fatebenefratelli-Sacco Infectious Diseases Physicians group; Radboud University Medical Center (RUMC) and COUGH1 study group
Collaborators, Affiliations

Comparative analysis of spike-specific IgG Fc glycoprofiles elicited by adenoviral, mRNA, and protein-based SARS-CoV-2 vaccines

Julie Van Coillie et al. iScience. .

Abstract

IgG antibodies are important mediators of vaccine-induced immunity through complement- and Fc receptor-dependent effector functions. Both are influenced by the composition of the conserved N-linked glycan located in the IgG Fc domain. Here, we compared the anti-Spike (S) IgG1 Fc glycosylation profiles in response to mRNA, adenoviral, and protein-based COVID-19 vaccines by mass spectrometry (MS). All vaccines induced a transient increase of antigen-specific IgG1 Fc galactosylation and sialylation. An initial, transient increase of afucosylated IgG was induced by membrane-encoding S protein formulations. A fucose-sensitive ELISA for antigen-specific IgG (FEASI) exploiting FcγRIIIa affinity for afucosylated IgG was used as an orthogonal method to confirm the LC-MS-based afucosylation readout. Our data suggest that vaccine-induced anti-S IgG glycosylation is dynamic, and although variation is seen between different vaccine platforms and individuals, the evolution of glycosylation patterns display marked overlaps.

Keywords: Glycomics; Immune response; Immunology; Microbiology.

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Conflict of interest statement

M.L.G. and R.R. are employees of Janssen Pharmaceuticals and M.L.G. is a shareholder in Johnson & Johnson. A.S. and W.A.d.J. are employees at AdaptVac, a company commercializing virus-like particle display technology and vaccines, including several patents. A.S., A.S., T.G.T., and M.N. are founders of AdaptVac and listed as coinventors on a patent covering the AP205 CLP vaccine platform technology (WO2016112921 A1) licensed to AdaptVac. Janssen Pharmaceuticals sponsored IgG glycosylation analysis at LUMC. Sanquin provided consultancy services to Janssen Pharmaceuticals during this study. All other authors declare they have no conflicts of interests.

Figures

None
Graphical abstract
Figure 1
Figure 1
Workflow of vaccine-induced antibody analysis by LC-MS and FEASI Upper panel: Longitudinal sampling regimen of study participants vaccinated with the various vaccine platforms. Middle panel: (left) Fucose-sensitive ELISA for anti-S IgG (FEASI) quantification (IgG ELISA) and FcγRIII-binding to anti-S specific IgG (FcγR-IgG ELISA) to determine IgG fucosylation; and (right) anti-S IgG1 glyco-profiling by liquid chromatography-mass spectrometry (LC-MS) by anti-S capture, wash, elution, digestion, LC-MS, and data extraction with LaCyTools., Lower panel: Influence of anti-S IgG1 Fc glycosylation traits on complement activation and FcγRIII binding.
Figure 2
Figure 2
Dynamics of anti-Spike IgG levels and IgG1 Fc glycosylation (A) Longitudinal anti-S IgG levels in Arbitrary Units (AU) per mL for all vaccines except for Janssen, which is expressed in Antibody Binding Units (ABU) per mL (thus not directly comparable with the other cohorts). The dotted horizontal line signifies the limit of detection. The solid horizontal line signifies the pre-outbreak threshold value as determined by pre-pandemic samples (95th percentile) (Figure S2). IgG1 Fc (B) fucosylation, (C) bisection, (D) galactosylation, and (E) sialylation for naive (circle, purple: one dose, blue: two doses) and antigen-experienced (orange triangle: two doses) vaccinees for Pfizer (n = 48), Moderna (n = 8), one (n = 39) or two (n = 39) doses Janssen (n = 78), AstraZeneca (n = 17), and RUMC/COUGH1 (n = 45). Range of the scheduled second vaccine dose is depicted vertically in gray. Previously published Pfizer data are included for comparative purposes. Statistical comparisons were conducted between the timepoints 2 weeks after 1st and 2 weeks after 2nd vaccination dose and are presented in Figures S4 and S6 for anti-S levels and glycosylation traits, respectively.
Figure 3
Figure 3
Total IgG1 Fc glycosylation is stable over time Longitudinal, total IgG1 Fc (A) fucosylation, (B) bisection, (C) galactosylation, and (D) sialylation for naive (circle, purple: one dose, blue: two doses) and antigen-experienced (orange triangle: two doses) vaccinees for Pfizer (n = 48), Moderna (n = 8), one (n = 39) or two (n = 39) doses Janssen (n = 78), AstraZeneca (n = 17), and RUMC/COUGH1 (n = 45). Range of the scheduled second vaccine dose is depicted vertically in gray. Previously published data were included for comparative purposes.
Figure 4
Figure 4
Anti-Spike IgG1 fucosylation level correlates with FcγRIIIa binding (A) Anti-S IgG binding to FcγRIIIa. (B) Anti-S fucosylation levels determined by FEASI for naive (blue circle) and antigen-experienced (orange triangle) vaccinees for Pfizer (n = 39), Moderna (n = 8), AstraZeneca (n = 17), and RUMC/COUGH1 (n = 45). (C) Spearman’s correlation of anti-S IgG fucosylation determined by FEASI and LC-MS for all available time points (circle: naive; triangle: antigen-experienced vaccinees). Color gradient indicates galactosylation level.
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