Delayed Induction of Noninflammatory SARS-CoV-2 Spike-Specific IgG4 Antibodies Detected 1 Year After BNT162b2 Vaccination in Children

Abstract

Humoral immune responses after BNT162b2 vaccination are predominantly composed of immunoglobulin (Ig) G1 and IgG3 subclass antibodies. As previously described in adults, S1-specific and receptor-binding domain-specific IgG4 levels increase significantly 1 year after the second BNT162b2 vaccination in children 5-11 years of age. Understanding mRNA vaccine-specific IgG4 responses in all age groups is crucial as more mRNA vaccines will reach licensure in the coming years.

Keywords: IgG subclass; IgG4; SARS-CoV-2; children; immune response; mRNA vaccine; noninflammatory; system immunology.

FIGURE 1.

Longitudinal IgG subclass composition of spike-specific antibodies following BNT162b2 vaccination in children. A and B: Subclass composition of (A) S1- and (B) RBD-specific IgG subclasses at baseline (V1D0), 4 weeks (V2D35) and 1 year (V2M12) after the second vaccination. Boxplots indicate median, IQR and min-max range. Dots represent individual study participants. C and D: Longitudinal dynamics of (C) S1- and (D) RBD-specific IgG4 induction. Connecting lines indicate data points belonging to the same study participant. All data points are reported as median fluorescent intensity (MFI), measured by the Bio-Plex 200 system. Fourteen children [median age, 8.5 (IQR, 6.4–10.0) years] received 2 doses of the mRNA-BNT162b2 vaccine (10 µg, Corminaty, BioNTech/Pfizer) with a median interval of 27.5 (IQR, 27–28) days; blood was collected on the day of the first dose (V1D0), as well as 5 weeks [V2D35; median, 35.5 (IQR, 30–45) days] and 1 year [V2M12; 350.5 (IQR, 344–364) days] after the second dose. Two individuals had been infected prior to V1D0 (indicated by black circles in C and D), and all previously uninfected children experienced breakthrough SARS-CoV-2-Omicron infection until V2M12. Statistical comparisons between V1D0, V2D35 and V2M12 are only shown for IgG4 subclasses, irrespective of statistical significance. Comparison over time within either the S1 or RBD group was done by the Kruskal-Wallis equality-of-populations rank test, followed by Dunn’s test, Bonferroni-adjusted for multiple comparisons (*P < 0.05; **P < 0.01; ***P < 0.001; and ****P < 0.0001). ns indicates not significant.