This article features the findings of a new preprint study: It was published two days ago by BioRxiv.
What is IgG4?
Antibodies are one of the body’s first defenses against an infection. Immunoglobulins (Ig) are another term for antibodies, and there are five types: IgG, IgA, IgM, IgD, and IgE.
IgM and IgG play a central role in infections. IgM comes out in the first few days, and IgG follows later.
IgG has four subclasses. IgG1, IgG2, IgG3 and IgG4. IgG1 and IgG3 play a big role in fighting infections. They attach to the microbes so the other parts of the immune system can identify and destroy them.
IgG2 and IgG4 do the opposite. They tone down the immune response. Hence, they promote immune tolerance. When people with severe allergies get desensitization therapy shots, the goal is to increase the IgG4 so that a severe reaction can be prevented when they get exposed again to the offending allergen.
Desensitization occurs with frequent exposure to a tiny amount of allergen (for example, bee venom or peanuts).
IgG4 increases with mRNA COVID shots
Previous studies have shown that IgG4 increases with the Pfizer COVID shot and Moderna COVID jab. I presented those studies in the following:
- Pfizer mRNA shots Switch Antibodies to Non-Neutralizing IgG4
- Moderna and Pfizer COVID jabs Increase Anti-inflammatory IgG4
IgG4 is not from the SARS-CoV-2, the virus that causes COVID-19. We know this because people with Long COVID Syndrome do not have an increase in IgG4.
IgG4 is not increased in Long COVID Syndrome.
Buhre and colleagues [4], who showed that the Moderna mRNA increases the IgG4, also showed that the AstraZeneca COVID shot, which uses adenovirus-vector technology rather than the lipid nanoparticle, does not increase the IgG4.
This brings us back to our featured study [1].
Hartley et al. are from Australia, where the AstraZeneca COVID shot was first approved for COVID-19. However, when AstraZeneca became associated with a severe clotting condition called VITT or Vaccine-Induced Thrombotic Thrombocytopenia, the Pfizer COVID jab became the preference for the first two injections (primary) and the booster doses.
VITT is a serious condition where a blood clot forms in the draining vessels of the brain and can lead to a brain bleed.
That is where the study comes in. In it, the authors answered the questions:
- What happens to the IgG4 if the first two shots are mRNA (Pfizer or Moderna) and the booster is another mRNA jab?
- If the first two shots are AstraZeneca, will the IgG4 increase if the booster dose is Pfizer or Moderna?
Here is the short answer.
IgG4 increases if the booster is an mRNA COVID shot in both situations. Whether the primary series are mRNA shots (Pfizer and Modrna) or vector-based injection (AstraZeneca), this is true.
How much IgG4 was produced?
So far, only a tiny percentage. The images below show the color-coded immunoglobulins.
Image C is the mRNA primary with an mRNA booster at different time points. D2 is the second dose, 6mD2 is six months after the second dose, D3 is when the booster shot was given, and 6mD3 is six months after the booster shot.
Image D is when the first two shots are AstraZeneca, and the booster jab is Pfizer. Note the absence of IgG4 (dark blue) in D2, 6mD2, and D3 and its appearance six months after the Pfizer shot. (6mD3)
Why does IgG4 increase only with the mRNA shots?
According to the authors, primary vaccination with the Pfizer BNT162b2 has a shorter window between dose one and dose 2 (3 weeks) than the AstraZeneca ChAdOx1 (12 weeks), and this may be a reason why more studies are needed.
My question is, how much will IgG4 increase further if more boosters are given? And if it does, is it good or bad?
This brings us to the comment by Shiv Pillai from the Ragon Institute of Massachusetts General Hospital, MIT, and Harvard. He wrote, Is it bad, is it good, or is IgG4 just misunderstood? [2]. Here is a quote.
There is evidence for the continued expression of spike mRNA for many months after mRNA vaccination and for the presumed expression of spike protein and the persistence of germinal centers also for many months.
Source: Is it bad, is it good, or is IgG4 just misunderstood?
There is continued expression or production of the spike protein of the SARS-CoV-2 for many months after the mRNA jab. Does that remind you of the desensitization therapy for allergies that was mentioned earlier?
Are the spike proteins in the cells of the vaccinated stimulating the increased production of IgG4? I think it does.
Shiv also answered, “Why exactly did a nonreplicating adenoviral vaccine not generate the same result?”
Most likely, the antigen levels achieved so far with two adenoviral vaccine doses have been inadequate to reach a threshold for enough IgG4 switching and accumulation.
Source: Is it bad, is it good, or is IgG4 just misunderstood?
In the end, Shiv wrote that IgG4 is good for humans “in general.”
Nevertheless, in general, even if this IgG subtype evolved in humans “by accident,” IgG4 antibodies in many contexts are clearly “good.”
They can neutralize effectively, they are transferred across the placenta, and they can contribute to dampening immunity.
They can compete with IgE and prevent anaphylaxis. They may even form small immune complexes and can certainly be a part of mixed immune complexes with IgG1.
Preventing higher IgG4
Shiv recommends preventing further increases in IgG4 in the context of the mRNA shots by getting boosters only once a year, smaller quantities of mRNA for booster doses, and using the mRNA injections for priming only.
Nonetheless, on the basis of the results of the studies discussed here and other theoretical considerations, future clinical studies need to evaluate the effectiveness of temporal spreading out of mRNA vaccine boosts—possibly no more than once a year.
Other approaches worth investigating would be the use of smaller quantities of mRNA for booster doses and, separately, the use of mRNA vaccines for priming only, with heterologous boosts with adjuvant-free recombinant spike proteins because, theoretically, adjuvants are most relevant during priming and may not be necessary for boosting.
Source: Is it bad, is it good, or is IgG4 just misunderstood?
My Two Cents
How about don’t get the COVID shots anymore? Just do early treatment. I already wrote what a high IgG4 can do.
- The Devastating Effects of IgG4 after the mRNA COVID Shots
- Three Studies Link High IgG4 to Severe COVID-19
I don’t want to discover the effects of an abnormally high IgG4 on myself. Do you?
Truth heals. Lies kill. Don’t Get Sick!
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- Pillai S. Is it bad, is it good, or is IgG4 just misunderstood? Sci Immunol. 2023 Mar 31;8(81):eadg7327. doi: 10.1126/sciimmunol.adg7327. Epub 2023 Mar 24. PMID: 36749191.
- Irrgang P, Gerling J, Kocher K, Lapuente D, Steininger P, Habenicht K, Wytopil M, Beileke S, Schäfer S, Zhong J, Ssebyatika G, Krey T, Falcone V, Schülein C, Peter AS, Nganou-Makamdop K, Hengel H, Held J, Bogdan C, Überla K, Schober K, Winkler TH, Tenbusch M. Class switch toward noninflammatory, spike-specific IgG4 antibodies after repeated SARS-CoV-2 mRNA vaccination. Sci Immunol. 2023 Jan 27;8(79):eade2798. doi: 10.1126/sciimmunol.ade2798. Epub 2023 Jan 27. PMID: 36548397; PMCID: PMC9847566.
- Buhre JS, Pongracz T, Künsting I, Lixenfeld AS, Wang W, Nouta J, Lehrian S, Schmelter F, Lunding HB, Dühring L, Kern C, Petry J, Martin EL, Föh B, Steinhaus M, von Kopylow V, Sina C, Graf T, Rahmöller J, Wuhrer M, Ehlers M. mRNA vaccines against SARS-CoV-2 induce comparably low long-term IgG Fc galactosylation and sialylation levels but increasing long-term IgG4 responses compared to an adenovirus-based vaccine. Front Immunol. 2023 Jan 12;13:1020844. doi: 10.3389/fimmu.2022.1020844. PMID: 36713457; PMCID: PMC9877300.
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