Post-Vaxx subclass switch associated with increased risk of COVID-19
Yet another serological study has replicated findings that we have all been noticing over the past couple of years in both serological and observational research of repeated modRNA transfections that is conducted for more than a few months. When observational research finds negative VE around the half year mark after the last booster what we are seeing is booster induced immune tolerance to the spike protein.
A longitudinal analysis and serological study of healthcare workers who participated in the Covid Cat Central cohort study, conducted in the Barcelona and Catalonia, enrolled during three different time points during the pandemic both before and after the vaxx rollout (n = 149) found that the expansion of non-cytophilic antibodies (IgG2 and G4) relative to cytophilic Immunoglobulin (IgG1 and IgG3) is associated with reduced antibody functionality specifically on the Fc gamma receptors and complement component 1Q. The ratio IgG4 to IgG1 rose from 2 months post primary series to 5 months post primary series while IgG3 began to decline 4 months post primary series and eventually returned to baseline levels. Over a 6 month follow-up period between June and December 2022, a higher ratio of non-cytophilic antibodies relative to cytophilic antibodies was ‘significantly associated with an increased risk of symptomatic disease in univariable time-to-event analysis.’ They also found that ‘the association between IgG4 levels and risk of infection remained significant, indicating that IgG4 associates with increased risk independent of IgG1 levels.’ Thus the increase in receptor binding domain and spike IgG4 antibodies itself increases the risk of a breakthrough infection among the vaxxed by decreasing FC effector functionality and the ability to form immune complexes. The authors note that similar findings of an Immunoglobulin G subclass switch following repeated boosters against malaria, HIV and pertussis are also associated with elevated disease risk.
Subclass switch is not inherent to spike protein exposure
The IgG subclass switch is not an inherent feature of exposure to the spike protein itself or a function of time since exposure. Tam and colleagues found no detectable spike specific IgG4 antibodies in the blood of a longitudinal infection cohort followed up to 33 weeks after their infection. However, after two breakthrough infections, following immunization with Pfizer’s modRNA transfection, they found a ‘robust’ spike specific IgG4 antibody response for at least 6 months after the second infection, but found no detectable anti-nucleocapsid IgG4 antibodies after a repeat infection even at the 6 month follow up period. This suggests ‘the class-switch to IgG4 is specific for SARS-CoV-2 spike in the form of an mRNA-based immunogen.’Their serological research also revealed no correlation between spike specific IgG4 antibody levels and antibody-dependent cellular phagocytosis, an important immune response for clearing virions and infected cells. Spike specific IgG4 can also reduce overall effector function activity when competing with spike specific IgG1 antibodies for binding to the receptor binding domain or N-terminal.
I have been cataloging such research in prior answers that I update continuously. I’ve noted in these prior answers that this subclass switch to a tolerogenic antibody response also does not appear to occur after repeat immunizations with either the recombinant spike protein (NOVAVAX) or adenoviral vector (AstraZeneca) platforms: only modRNA transfections.
Answer: What Makes the modRNA COVID-19 Shots so Effective?
Answer: Why does it seem like the COVID shots only partially work
Answer: Is a booster dose of the Covid vaccine necessary for longer-lasting immunity?
Answer: How many vaccinations do you need to become immune to Covid19?
As I mentioned in another prior answer this subclass switch also appears to mediate antibody dependent enhancement of disease and predicts higher COVID-19 mortality among hospitalized patients.