The BNT162b2 mRNA SARS-CoV-2 vaccine induces transient afucosylated IgG1 in naive but not in antigen-experienced vaccinees

Coillie, Julie Van; Pongrácz, Tamás; Rahmöller, Johann; Chen, Hung Jen; Geyer, Chiara E.; Vught, Lonneke A. van; Buhre, Jana Sophia; Šuštić, Tonći; Osch, Thijs L. J. van; Steenhuis, Maurice; Hoepel, Willianne; Wang, Wenjun; Lixenfeld, Anne Sophie; Nouta, Jan; Keijzer, Sofie; Linty, Federica; Visser, Remco; Larsen, Mads Delbo; Martin, Emily; Künsting, Inga; Lehrian, Selina; Kopylow, Vera von; Kern, Carsten; Lunding, Hanna B.; Winther, Menno P.J. de; Mourik, Niels van; Rispens, Theo; Graf, Tobias; Minnaar, R. P.; Schoot, C. Ellen van der; Dunnen, Jeroen den; Wuhrer, Manfred; Ehlers, Marc; Vidarsson, Gestur; Antinori, Spinello; Bassoli, Cinzia; Bestetti, Giovanna; Corbellino, Mario; Covizzi, Alice; Lupo, A; Milazzo, Laura; Schiuma, Marco; Torre, Alessandro; Appelman, Brent; de, Diederik Beek van; Bomers, Marije; de, Justin Brabander; Brouwer, Matthijs C.; Buis, David T.P.; Chekrouni, Nora; van, Marit J. Gils; de, Menno D. Jong; Lavell, Ayesha H.A.; van, Niels Mourik; Olie, Sabine E.; Peters, Edgar J.G.; Reijnders, Tom D.Y.; Schinkel, Michiel; Schuurman, Alex R.; Sikkens, Jonne J.; Slim, Marleen A.; Smulders, Yvo M.; Vlaar, Alexander P.J.; van, Lonneke A. Vught; Wiersinga, Joost W.

doi:10.1016/j.ebiom.2022.104408

Cited by 18 publications

(43 citation statements)

References 57 publications

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“…Next, we analyzed anti-S1 serum IgG subclass abundances over time ( Figures 2 , S2 , S3 ). Our observations confirmed recent findings describing that the mRNA vaccines initially induce anti-S1 IgG1 followed by IgG3 and IgG2 and hardly any IgG4 responses ( 31 , 32 , 34 ), whereas vaccination with AZD1222 mainly results in anti-S IgG1 and IgG3, but hardly any IgG2 and IgG4 ( 5 ) in the first weeks after immunization of naïve individuals ( Figures 2 , S2 , S3 ).…”

Section: Resultssupporting

confidence: 92%

“…In line with recent findings, the first immunization with BNT162b2 induced an initial anti-S IgG1 response with a temporarily afucosylated glycosylation pattern, with fucosylation levels as low as 80% ( 34 ) ( Figures 4B , S5 ). The fucosylation levels steadily increased in the next few weeks to about 98%, surpassing the corresponding total IgG1 fucosylation levels (92-94%), and stagnated over the study period ( Figures 4B , S5 , S6 ).…”

Section: Resultssupporting

confidence: 91%

“…First, we analyzed anti-S1 serum IgG Ab levels by commercially available (EUROIMMUN) and in-house developed (HL) ELISA methods ( Figures 1A–D , S1 ). Early anti-S1 serum IgG levels of naïve and pre-infected vaccinees were similar to those described earlier ( 9 , 31 , 34 , 68 ). All three vaccines induced higher anti-S1 serum IgG levels after the second as compared to the first vaccination indicating a re-activation of memory B cells ( Figures 1A , S1 ).…”

Section: Resultssupporting

confidence: 85%

“…In contrast, BNT162b2-vaccinated non-hospitalized pre-infected individuals maintained stable anti-S IgG1 fucosylation levels over time (96-97%), which was lower than the long-term anti-S IgG1 fucosylation level of naïve vaccinees and might have had developed already before vaccination as hypothesized previously ( 34 ) ( Figures 4D , S5 , S6 ). In comparison, the early, very low anti-S IgG1 fucosylation levels (down to 70% fucosylation) of the unvaccinated hospitalized patients vastly increased and reached fucosylation levels higher than 95% already 50 days post-infection ( 60 ) ( Figure 4E ).…”

Section: Resultsmentioning

confidence: 51%

“…The new mRNA vaccines against SARS-CoV-2 generate an initial anti-S and -RBD IgG (1) Ab response with transient afucosylation, but high galactosylation and sialylation levels ( 32 , 34 , 35 ).…”

Section: Introductionmentioning

confidence: 99%

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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

et al. 2023

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BackgroundThe 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.ObjectiveHowever, 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.MethodsHere, 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.ResultsWe 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.ConclusionIn 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 TH1-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.

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Section: Resultssupporting

confidence: 92%

Section: Resultssupporting

confidence: 91%

Section: Resultssupporting

confidence: 85%

Section: Resultsmentioning

confidence: 51%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

et al. 2023

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SARS‐CoV‐2 infection triggers more potent antibody‐dependent cellular cytotoxicity (ADCC) responses than mRNA‐, vector‐, and inactivated virus‐based COVID‐19 vaccines

Zedan,

Smatti,

Al‐Sadeq

et al. 2024

Journal of Medical Virology

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Neutralizing antibodies (NAbs) are elicited after infection and vaccination and have been well studied. However, their antibody‐dependent cellular cytotoxicity (ADCC) functionality is still poorly characterized. Here, we investigated ADCC activity in convalescent sera from infected patients with wild‐type (WT) severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) or omicron variant compared with three coronavirus disease 2019 (COVID‐19) vaccine platforms and postvaccination breakthrough infection (BTI). We analyzed ADCC activity targeting SARS‐CoV‐2 spike (S) and nucleocapsid (N) proteins in convalescent sera following WT SARS‐CoV‐2‐infection (n = 91), including symptomatic and asymptomatic infections, omicron‐infection (n = 8), COVID‐19 vaccination with messenger RNA‐ (mRNA)‐ (BNT162b2 or mRNA‐1273, n = 77), adenovirus vector‐ (n = 41), and inactivated virus‐ (n = 46) based vaccines, as well as post‐mRNA vaccination BTI caused by omicron (n = 28). Correlations between ADCC, binding, and NAb titers were reported. ADCC was elicited within the first month postinfection and ‐vaccination and remained detectable for ≥3 months. WT‐infected symptomatic patients had higher S‐specific ADCC levels than asymptomatic and vaccinated individuals. Also, no difference in N‐specific ADCC activity was seen between symptomatic and asymptomatic patients, but the levels were higher than the inactivated vaccine. Notably, omicron infection showed reduced overall ADCC activity compared to WT SARS‐CoV‐2 infection. Although post‐mRNA vaccination BTI elicited high levels of binding and NAbs, ADCC activity was significantly reduced. Also, there was no difference in ADCC levels across the four vaccines, although NAbs and binding antibody titers were significantly higher in mRNA‐vaccinated individuals. All evaluated vaccine platforms are inferior in inducing ADCC compared to natural infection with WT SARS‐CoV‐2. The inactivated virus‐based vaccine can induce N‐specific ADCC activity, but its relevance to clinical outcomes requires further investigation. Our data suggest that ADCC could be used to estimate the extra‐neutralization level against COVID‐19 and provides evidence that vaccination should focus on other Fc‐effector functions besides NAbs. Also, the decreased susceptibility of the omicron variant to ADCC offers valuable guidance for forthcoming efforts to identify the specific targets of antibodies facilitating ADCC.

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Bulk IgG glycosylation predicts COVID-19 severity and vaccine antibody response

et al. 2022

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The BNT162b2 mRNA SARS-CoV-2 vaccine induces transient afucosylated IgG1 in naive but not in antigen-experienced vaccinees

Cited by 18 publications

References 57 publications

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

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

SARS‐CoV‐2 infection triggers more potent antibody‐dependent cellular cytotoxicity (ADCC) responses than mRNA‐, vector‐, and inactivated virus‐based COVID‐19 vaccines

Bulk IgG glycosylation predicts COVID-19 severity and vaccine antibody response

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