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Notes -
“Even a stopped clock...”
Neat paper, though.
IgG4 antibodies among all spike-specific IgG antibodies rose on average from 0.04% shortly after the second vaccination to 19.27% late after the third vaccination.
This induction of IgG4 antibodies was not observed after homologous or heterologous SARS-CoV-2 vaccination with adenoviral vectors. [is that traditional vaccination?]
...this class switch was associated with a reduced capacity of the spike-specific antibodies to mediate antibody-dependent cellular phagocytosis and complement deposition.
Furthermore, we observed significantly higher IgG4 levels after two doses of Comirnaty [Pfizer] mRNA vaccine compared to a heterologous immunization regimen with a primary Vaxzevria vaccination followed by one dose of Comirnaty, although the total anti-spike IgG response was comparable.
Once infection is established, Fc-mediated effector functions become more relevant to clear viral infections.
Since Fc-mediated effector function could be critical for viral clearance, an increase in IgG4 subclasses might result in longer viral persistence in case of infection.
However, it is also conceivable that non-inflammatory Fc-mediated effector functions reduce immunopathology while virus is still being neutralized via high-avidity antibody variable regions.
Some percentage of antibodies end up as IgG4, which may reduce effectiveness at clearing an infection once it gets established. This could be a real problem with effectiveness!
My eyes on this for sure. It makes sense that a vaccine vector that can enter the blood stream and deploy (mRNA nanolipid) is acting like an allergy shot.
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Depends what you mean by "traditional", but not really. I would describe viral vector vaccines as more tested than mRNA vaccines, but they still haven't made much end-use impact. What I would personally describe as a traditional vaccine would be any of:
Attenuated pathogens, such as the MMR vaccine.
Inactivated pathogens, such as the old whole-cell pertussis vaccine.
Antigen and adjuvant, such as the newer acellular pertussis vaccine.
This may also be a marker for something even weirder (maybe worse) going on - IgG4 can be associated with immune tolerance and anti-inflammatory responses. If additional boosts skew even further, this could be a real concern.
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