"Abstract
Background: Previous research has shown that repeated COVID-19 mRNA vaccination leads to a marked increase of SARS-CoV-2 spike-specific serum antibodies of the IgG4 subclass, indicating far-reaching immunoglobulin class switching after booster immunization. Considering that repeated vaccination has been recommended especially for older adults, the aim of this study was to investigate IgG subclass responses in the ageing population and assess their relation with Fc-mediated antibody effector functionality...
Conclusions: In conclusion, these findings show that, like younger individuals, older adults produce antibodies with reduced functional capacity upon repeated COVID-19 mRNA vaccination. Additional research is needed to better understand the mechanisms underlying these responses and their potential implications for vaccine effectiveness...
Background
... Importantly, structural features of the IgG4 (and IgG2) Fc-tail also result in poor binding to activating Fc receptors (FcR) and complement, resulting in a very limited capacity to engage in Fc-mediated effector functions... Increasing evidence suggests that Fc-mediated antibody effector functions contribute to immunological protection from disease upon SARS-CoV-2 and other viral infections...
Well known Fc-mediated effector functions are antibody-dependent cellular phagocytosis (ADCP), complement deposition (ADCD), and cellular cytotoxicity (ADCC) by natural killer (NK) cells...
Discussion
... In this study, we have shown that considerable class switching to IgG4 also occurs in older adults upon repeated mRNA vaccination and that IgG4 levels following the fifth vaccine dose even exceed those induced after the third dose. Furthermore, our data show that the increased ratio of IgG4/IgG1 following repeated vaccination associates with a reduced capacity of the virus-specific antibodies to mediate NK cell activation and complement deposition relative to total virus-specific IgG concentrations.
Previously, we have also observed a decline in antibody-dependent NK cell activation relative to antibody concentration over time following primary SARS-CoV-2 infection in children and adults."
© The Author(s) 2024.
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