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

作者：Jana Sophia Buhre, Tamás Pongrácz, Inga Künsting, Anne S. Lixenfeld, Wenjun Wang, Jan Nouta, Selina Lehrian, Franziska Schmelter, Hanna B. Lunding, Lara Dühring, Carsten Kern, Janina Petry, Emily Martin, Bandik Föh, Moritz Steinhaus, Vera von Kopylow, Christian Sina, Tobias Graf, Johann Rahmöller, Manfred Wuhrer, Marc Ehlers · 发表于：Frontiers in Immunology · 年份：2023 · DOI：10.3389/fimmu.2022.1020844 · 被引用次数：99 · 研究领域：Monoclonal and Polyclonal Antibodies Research、Glycosylation and Glycoproteins Research、vaccines and immunoinformatics approaches

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 pr...