What happens if our immune system is exposed to high level doses of the same antigen? For example, with the COVID mRNA “vaccines,” some people are now on their fifth dose. Are there any negative effects of being exposed to the same antigen with such high frequency?
The first thing to consider is the response of our immune system with each additional dose. The first dose trains our B Cells and T Cells to recognize and launch an immune attack upon subsequent exposures to the Spike protein, When our cells are coaxed to produce Spike protein a second time when the second dose is administered, our immune system is primed and ready to immediately attack the cells which are synthesizing the Spike protein. In other words, whatever tissues are synthesizing the Spike protein are now seen as foreign, and our immune system deals with those tissues accordingly. This is most likely why several studies show that the risk of adverse events dramatically increases with the second dose.
To take those Spike-synthesizing cells out of commission, the immune system will respond with Antibody-Dependent Complement-Mediated Lysis (ADCML), Antibody Dependent Cellular Phagocytosis (ADCP), Antibody Dependent Cellular Cytotoxicity (ADCC), and Cytotoxic T Cells. This leads to inflammation and tissue damage at the locations of Spike Protein production. For example, if the lipid nanoparticles cross the blood brain barrier, and the tissue inside of your brain begins synthesizing the Spike protein, your immune cells will attack your brain tissue. If the endothelial cells lining your blood vessels produce the Spike protein, then they are the target for destruction. It all depends on where the vaccine lipid nanoparticles carrying the mRNA happen to .travel, and which cells begin synthesizing Spike protein.
In addition to Spike being presented by cells, Spike protein that is freely circulating in blood plasma can bind with antibodies and create Circulating Immune Complexes (CICs) which can deposit and lead to tissue damage, platelet activation, inflammation of blood vessels, and thrombosis.
What about the nature of the immune response itself? Will the immune response change with repeated exposures to the same antigen? It appears that the answer is yes. New research shows that the type of antibody radically shifts upon the 3rd dose of mRNA. One potential implication of this antibody switch is losing the ability to launch a viable immune response against future infections.
There are four subtypes of IgG antibodies, labeled IgG1, IgG2, IgG3, and IgG4. By far, IgG1 is the predominant subclass of antibody which is present after an infection. IgG1 antibodies can neutralize an infection, and also help clear an infection.
In a new paper (linked below), they show the normal IgG1 response after the first 2 doses, but after the third dose an unusual and sharp increase in IgG4 is observed in almost all vaccine recipients. An IgG4 response is normally not seen with other vaccines or repeated infections. IgG4 has been observed in some people with a COVID infection early in the pandemic, but this rise in IgG4 is associated with poor/severe outcome.
IgG4 is a non-inflammatory antibody, with the ability to bind and neutralize soluble or membrane bound spike protein. However, unlike IgG1 antibodies, IgG4 are terrible at launching effector functions that mobilize cellular clearance of the virus.
More specifically, IgG4 exhibits decreased Fc-mediated antibody effector functions including decreased antibody-dependent cellular phagocytosis (ADCP), cellular cytotoxicity (ADCC) and complement deposition (ADCD). These are required to help with viral clearance.
If repeated booster doses further skew the antibody pool towards IgG4, this could translate into an impaired ability to clear future infections.
This is highly unusual. IgG4 is normally expressed when a non infectious antigen/allergen is presented to the body repeatedly over a long time. This is how the immune system builds up tolerance. IgG4 binds to the antigen and blocks other antibodies from launching a full blown immune defense. You may want this type of immune response if you’re presented with an allergen, but this is not the type of immune response that will effectively clear a viral infection.
There’s almost always a small percentage of IgG4 antibodies that are present in an infectious response (4-6%), so the presence of IgG4 is not abnormal. It’s the ratio of IgG4 to IgG1 that matters, and this ratio is highly skewed towards IgG4 on the 3rd dose. In this study, IgG4 increases from 0.04% of the total IgG pool, to 19.27% of the total IgG pool after the 3rd dose of the mRNA vaccine. This is highly unusual and concerning, since this high IgG4/IgG1 ratio has the potential to block the totality of the immune response elicited by the other IgG’s.
Quotes from the Paper:
“In our study, antibody-mediated phagocytic activity and complement deposition were reduced in sera after the third immunization, in parallel to higher proportions of anti-spike IgG4 antibodies.”
“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.”
“In a cohort of vaccinees with breakthrough infections, we did not obtain any evidence for an alteration of disease severity, which was mild in almost all of our cases. Larger cohorts with differential disease severities will be needed to address this aspect in the future.” (Their sample size was small)
“Nevertheless, a Brazilian study during the early phase of the pandemic correlated an early onset and high levels of anti-spike IgG4 antibodies with a more severe COVID-19 progression after SARS-CoV-2 infection, which might indicate a less effective antibody response.”
“Additionally, Della-Torre et al. reported on a significant association of high IgG4/IgG1 ratios with poor disease outcome.”
Considering all of the above, what is the point of receiving multiple doses of the vaccine, if the chances of adverse events significantly increase with each dose, and the antibody class switches such that the immune system now tolerates the virus? Will people who continue to receive repeated boosters be unable to clear the virus due to immune tolerance? Considering the preponderance of studies that demonstrate natural immunity is robust and effective, what is the justification for repeated rounds of the jabs?
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“Class switch toward noninflammatory, spike-specific IgG4 antibodies after repeated SARS-CoV-2 mRNA vaccination”