Spike-specific IgG4 generated post BNT162b2 mRNA vaccination is inhibitory when directly competing with functional...

Area of Science:

• Immunology
• Vaccinology
• Virology

Background:

• COVID-19 vaccines are crucial for pandemic control.
• Spike-specific antibodies, including neutralizing and effector-function types, are key to vaccine protection.
• Elevated Spike-specific immunoglobulin G4 (IgG4) levels have been observed post-mRNA vaccination.

Purpose of the Study:

• To investigate the factors influencing Spike-specific IgG4 levels after BNT162b2 vaccination.
• To assess the functional impact of Spike-specific IgG4 in the context of other antibody subclasses.

Main Methods:

• Analysis of Spike-specific IgG subclasses (IgG1-IgG4) following BNT162b2 vaccination.
• Evaluation of effector functions like antibody-dependent cellular cytotoxicity (ADCC) and complement deposition (ADCD).
• Assessment of IgG4's inhibitory potential in competition with functional IgG subclasses.

Main Results:

• Spike-specific IgG4 levels are influenced by vaccination intervals, infection history, and booster types.
• IgG4 exhibits reduced effector functions (ADCC, ADCD, phagocytosis).
• IgG4's inhibitory effect is observed only when it competes with functional IgG subclasses for overlapping epitopes.

Conclusions:

• The impact of Spike-specific IgG4 on vaccine-induced immunity is context-dependent.
• The non-stimulatory effect of IgG4 might be masked within polyclonal antibody mixtures.
• Understanding IgG4 dynamics is important for optimizing vaccine strategies.