Repeated doses of mRNA vaccines bias the antibody response to an IgG4 subtype with a reduction in some effector functions. What does that actually mean for future #COVID19 vaccine policy?
Helpful commentary by the legendary Shiv Pallai: is it bad, is it good, or is IgG4 just misunderstood?
1)The Nucleocapsid is highly pernicious. Dysregulated Antibody Dependent Complement Mediated Lysis of the SARS-CoV-2 virion is the cause of Severe Disease for the overwhelming majority of those afflicted.
IgG4 discourages ADCML relative to other subtypes because it has the lowest affinity for C1q. This encourages Antibody Dependent Cellular Phagocytosis by default.
However, this is an indirect effect as Spike ABs don't necessarily effect lysis of the
2)lipid portion of the viral envelope. That falls to M-protein ABs. Still, decreased demand on C1-INH by that IgG4 is going to make more C1-INH available in the microenvironment to slow down M-protein dependent ADCML, so it is still a win.
What would be really nice is IgG4 on the M-protein epitopes. Or better yet, aptamers without FCs altogether.
I'm still a little slow with all of the immunology ins and outs but I got there. Thank you for the thoughts, as always!
