Class switch toward noninflammatory, spike-specific IgG4 antibodies after repeated SARS-CoV-2 mRNA vaccination
Anti-spike IgG4 rises from obscurity
The four human IgG subclasses have distinct effector properties due to differences in binding Fc receptors and activating complement. The serum concentration of human IgG4 is normally lower than either IgG1, IgG2, or IgG3. Irrgang et al. did a longitudinal analysis of the level of spike-specific antibodies from each IgG subclass in recipients of the SARS-CoV-2 BNT162b2 mRNA vaccine. Anti-spike IgG4 as a fraction of total anti-spike IgG rose by 6 months after the second vaccination and increased further after a third vaccine dose. Serum antibody effector activity assessed by antibody-dependent phagocytosis or complement deposition was less after the third dose than after the second dose. Further studies are needed to determine how emergence of an IgG4 anti-spike response influences vaccine-induced protection from SARS-CoV-2 infection. —IRW