mRNA vaccines against SARS-CoV-2 induce comparably low long-term IgG Fc galactosylation and sialylation levels but increasing long-term IgG4 responses compared to an adenovirus-based vaccine.

Autor:	Buhre JS; Laboratories of Immunology and Antibody Glycan Analysis, Institute of Nutritional Medicine, University of Lübeck and University Medical Center Schleswig-Holstein, Lübeck, Germany., Pongracz T; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands., Künsting I; Laboratories of Immunology and Antibody Glycan Analysis, Institute of Nutritional Medicine, University of Lübeck and University Medical Center Schleswig-Holstein, Lübeck, Germany., Lixenfeld AS; Laboratories of Immunology and Antibody Glycan Analysis, Institute of Nutritional Medicine, University of Lübeck and University Medical Center Schleswig-Holstein, Lübeck, Germany., Wang W; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands., Nouta J; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands., Lehrian S; Laboratories of Immunology and Antibody Glycan Analysis, Institute of Nutritional Medicine, University of Lübeck and University Medical Center Schleswig-Holstein, Lübeck, Germany., Schmelter F; Institute of Nutritional Medicine, University of Lübeck and University Medical Center Schleswig-Holstein, Lübeck, Germany., Lunding HB; Laboratories of Immunology and Antibody Glycan Analysis, Institute of Nutritional Medicine, University of Lübeck and University Medical Center Schleswig-Holstein, Lübeck, Germany., Dühring L; Laboratories of Immunology and Antibody Glycan Analysis, Institute of Nutritional Medicine, University of Lübeck and University Medical Center Schleswig-Holstein, Lübeck, Germany., Kern C; Laboratories of Immunology and Antibody Glycan Analysis, Institute of Nutritional Medicine, University of Lübeck and University Medical Center Schleswig-Holstein, Lübeck, Germany., Petry J; Laboratories of Immunology and Antibody Glycan Analysis, Institute of Nutritional Medicine, University of Lübeck and University Medical Center Schleswig-Holstein, Lübeck, Germany., Martin EL; Laboratories of Immunology and Antibody Glycan Analysis, Institute of Nutritional Medicine, University of Lübeck and University Medical Center Schleswig-Holstein, Lübeck, Germany., Föh B; Institute of Nutritional Medicine, University of Lübeck and University Medical Center Schleswig-Holstein, Lübeck, Germany., Steinhaus M; Laboratories of Immunology and Antibody Glycan Analysis, Institute of Nutritional Medicine, University of Lübeck and University Medical Center Schleswig-Holstein, Lübeck, Germany.; Department of Anesthesiology and Intensive Care, University of Lübeck and University Medical Center Schleswig-Holstein, Lübeck, Germany., von Kopylow V; Laboratories of Immunology and Antibody Glycan Analysis, Institute of Nutritional Medicine, University of Lübeck and University Medical Center Schleswig-Holstein, Lübeck, Germany., Sina C; Institute of Nutritional Medicine, University of Lübeck and University Medical Center Schleswig-Holstein, Lübeck, Germany., Graf T; Medical Department 2, University Heart Center of Schleswig-Holstein, Lübeck, Germany., Rahmöller J; Laboratories of Immunology and Antibody Glycan Analysis, Institute of Nutritional Medicine, University of Lübeck and University Medical Center Schleswig-Holstein, Lübeck, Germany.; Department of Anesthesiology and Intensive Care, University of Lübeck and University Medical Center Schleswig-Holstein, Lübeck, Germany., Wuhrer M; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands., Ehlers M; Laboratories of Immunology and Antibody Glycan Analysis, Institute of Nutritional Medicine, University of Lübeck and University Medical Center Schleswig-Holstein, Lübeck, Germany.; Airway Research Center North (ARCN), University of Lübeck, German Center for Lung Research (DZL), Lübeck, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Jan 12; Vol. 13, pp. 1020844. Date of Electronic Publication: 2023 Jan 12 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.1020844
Abstrakt:	Background: The new types of mRNA-containing lipid nanoparticle vaccines BNT162b2 and mRNA-1273 and the adenovirus-based vaccine AZD1222 were developed against SARS-CoV-2 and code for its spike (S) protein. Several studies have investigated short-term antibody (Ab) responses after vaccination. Objective: However, the impact of these new vaccine formats with unclear effects on the long-term Ab response - including isotype, subclass, and their type of Fc glycosylation - is less explored. Methods: Here, we analyzed anti-S Ab responses in blood serum and the saliva of SARS-CoV-2 naïve and non-hospitalized pre-infected subjects upon two vaccinations with different mRNA- and adenovirus-based vaccine combinations up to day 270. Results: We show that the initially high mRNA vaccine-induced blood and salivary anti-S IgG levels, particularly IgG1, markedly decrease over time and approach the lower levels induced with the adenovirus-based vaccine. All three vaccines induced, contrary to the short-term anti-S IgG1 response with high sialylation and galactosylation levels, a long-term anti-S IgG1 response that was characterized by low sialylation and galactosylation with the latter being even below the corresponding total IgG1 galactosylation level. Instead, the mRNA, but not the adenovirus-based vaccines induced long-term IgG4 responses - the IgG subclass with inhibitory effector functions. Furthermore, salivary anti-S IgA levels were lower and decreased faster in naïve as compared to pre-infected vaccinees. Predictively, age correlated with lower long-term anti-S IgG titers for the mRNA vaccines. Furthermore, higher total IgG1 galactosylation, sialylation, and bisection levels correlated with higher long-term anti-S IgG1 sialylation, galactosylation, and bisection levels, respectively, for all vaccine combinations. Conclusion: In summary, the study suggests a comparable "adjuvant" potential of the newly developed vaccines on the anti-S IgG Fc glycosylation, as reflected in relatively low long-term anti-S IgG1 galactosylation levels generated by the long-lived plasma cell pool, whose induction might be driven by a recently described T H1 -driven B cell response for all three vaccines. Instead, repeated immunization of naïve individuals with the mRNA vaccines increased the proportion of the IgG4 subclass over time which might influence the long-term Ab effector functions. Taken together, these data shed light on these novel vaccine formats and might have potential implications for their long-term efficacy. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Buhre, Pongracz, Künsting, Lixenfeld, Wang, Nouta, Lehrian, Schmelter, Lunding, Dühring, Kern, Petry, Martin, Föh, Steinhaus, von Kopylow, Sina, Graf, Rahmöller, Wuhrer and Ehlers.)
Databáze:	MEDLINE
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