Pfizer mRNA shots Switch Antibodies to Non-Neutralizing IgG4

A new peer-reviewed research showed that the Pfizer mRNA COVID shot could switch neutralizing antibodies to a non-inflammatory type, IgG4.

The study may explain why vaccinated individuals have breakthrough infections and why Long COVID syndrome happens.

Let’s start with a brief background that is relevant to the study

Immunoglobulins

Antibodies are also known as immunoglobulins. They are typically depicted as Y-shaped. The arms above are the Fab (fragment antigen-binding) portion that adheres to an antigen. And the Fc (fragment crystallizable), the bottom part, sticks to an effector molecule.

Source: By Tokenzero – Own work, based on File: Immunoglobulin basic unit. svg by Y_tambe, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=93798019Effector molecules do antibody-dependent cellular cytotoxicity (ADCC) or antibody-dependent cellular phagocytosis (ADCP). The Fc part also activates the complement system.

The ADCC, ADCP, and complement systems are all needed to kill germs and are affected by the type of antibody to which they are attached.

Immunoglobulin subclasses

There are different classes of antibodies or immune globulins. They are immunoglobulin G, A, M, D, and E. (IgG, IgA, IgM, IgD, and IgE)

IgG has four subclasses IgG1, IgG2, IgG3, and IgG4. All have different Fab and Fc portions to serve different purposes.

IgG1 and IgG3 are pro-inflammatory. This means they activate other immune cells like the macrophage to stimulate phagocytosis and the complement system. Both are essential to kill microbes.

In contrast, Ig4 is non-inflammatory. IgG4 is produced in response to non-microbial antigens like peanuts and bee stings. An allergen is an antigen that causes allergies.

If a person has life-threatening responses to an allergen like if the throat closes or if very low blood pressure happens, they are candidates for desensitization therapy.

Allergy desensitization is the introduction of small doses of antigens into the skin or under the tongue. The process takes months to years.

The idea is to gradually expose the immune system to the allergen so that the body will tolerate the same antigen in future exposures and avoid a life-threatening situation.

IgG4 is the antibody responsible for tolerance and shows up after allergy desensitization. That is why IgG4 is considered non-inflammatory or anti-inflammatory.

B cells produce antibodies

Immunoglobulins are produced by memory B cells that keep a record of germs that the body encounters. The memory of previously encountered viruses or bacteria serves as a “template” to make specific antibodies for them.

Once encountered again, the specific antibodies will be produced more rapidly and shorten the disease.

With that background, let’s go to the study.

Pfizer shot causes Class Switch to IgG4

The study authors are from several universities in Germany. The paper, Class switch towards non-inflammatory, spike-specific IgG4 antibodies after repeated SARS-CoV-2 mRNA vaccination, was published in Science Immunology on Dec 22, 20022.[1]

In their study, they found that several months after the second Pfizer COVID shot, the IgG4 begins to appear at 0.04%. One hundred eighty days after the third shot or breakthrough infection, the IgG4 increased to 19.27% of the total antibodies produced.

Although it may seem that the increase of IgG4 depends on the number of mRNA shots, they explain that the germinal cells that produce the IgG4 take a few months to mature to make the IgG4 cells.

That means the IgG4 level can be expected to be eventually high in people who had two doses of the Pfizer injections. In four individuals, IgG4 became the most prominent IgG subclass after the third immunization.

IgG4 antibodies accounted for 40–80% of all anti-Spike antibodies in individuals with a breakthrough infection.

Meanwhile, the levels of the other IgG subclasses, like the IgG1 and IgG3, dropped significantly, as expected.

IgG4-B cells were also produced

The study found an increase in memory B cells that produce IgG4.

Single-cell sequencing and flow cytometry revealed substantial frequencies of IgG4-switched B cells within the spike-binding memory B-cell population (median 14.4%; interquartile range (IQR) 6.7–18.1%) compared to the overall memory B-cell repertoire (median 1.3%; IQR 0.9–2.2%) after three immunizations.

In contrast, the B cells producing IgG3 against SARS-CoV-2, the ones needed to prevent COVID-19, were barely detectable.

Phagocytosis and Complement Effects are Reduced with IgG4

Phagocytosis is the process where neutrophils and macrophages ingest a microbe. It does two things. It gets rid of the germ, and the microbe’s antigens get processed and presented to the adaptive immune system.

The complement system is a series of molecular reactions that result in the killing of germs.

In the research, the authors found that the IgG4s that were produced decreased the level of phagocytosis and the action of the complement system.

Thus, high levels of IgG4 significantly decreased the infection-stopping response of the ADCC, ADCP, and complement system to SARS-CoV-2.

Breakthrough infections Increase IgG4

It is not only the mRNA shots that increased the IgG4. In a group of people that had the mNA shots and then had breakthrough infections, they found that they also had higher levels of IgG4.

Our results clearly demonstrate that a subsequent infection can further boost IgG4 antibody levels, with IgG4 becoming the most dominant among all anti-spike IgG subclasses in some individuals.

If you wonder whether the same effect happens in other vaccines, the authors looked into that.

The IgG4 subclass does not prevail after repeated vaccination with tetanus toxoid or RSV infections

This time, 23 volunteers with several tetanus toxoid vaccines and another ten were tested for antibodies against the respiratory syncytial virus (RSV) that is known to reinfect humans several times.

The tetanus toxoid group had low levels of IgG4 antibodies with no correlation to the number of vaccinations. IgG4 was not found in the RSV group.

They also found that class switching to IgG4 was not observed with the AstraZeneca COVID-19 shots.

Bottomline: An increase in IgG4 is not an expected result of vaccinations.

Whether the increase in IgG4 also happens in the Moderna mRNA shot remains to be seen in another study. I presume that the Moderna shot can also increase the IgG4.

My comment

Pfizer uses neutralizing antibody levels elicited after the shots to proclaim that their “vaccine” is effective. This study shows that, with time, not all antibodies can effectively remove the virus because of the significant amount of non-inflammatory IgG4 produced.

Added Mar. 2, 2023: Moderna and Pfizer COVID jabs Increase Anti-inflammatory IgG4

The IgG4 levels explain many previous findings about breakthrough infections, autoimmune diseases following COVID and its shots, and Long COVID.

The IgG4 antibodies produced after the mRNA shots tolerate SARS-CoV-2 and prevent its total elimination. However, the remaining pro-inflammatory immune system can tip the balance, or the virus can overwhelm the immune system and lead to severe illness and death.

The study also explains why breakthrough infections happen to those with the shots.

And why the vaccinated carry SARS-CoV-2.

The effect of the remaining SARS-CoV-2 may result in a persistent, smoldering inflammation like Long COVID.

Or an autoimmune response.

With that in mind, it is better to use an effective antiviral when faced with COVID-19.

And to optimize the immune system.

Here are some helpful protocols from the Front Line COVID-19 Critical Care Alliance

Truth heals. Lies kill. Don’t Get Sick!

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Reference:

Irrgang P et al. Class switch towards non-inflammatory, spike-specific IgG4 antibodies after repeated SARS-CoV-2 mRNA vaccination. SCIENCE IMMUNOLOGY. Dec 22, 2022. DOI: 10.1126/sciimmunol.ade2798
Vidarsson G, Dekkers G, Rispens T. IgG subclasses and allotypes: from structure to effector functions. Front Immunol. 2014 Oct 20;5:520. doi: 10.3389/fimmu.2014.00520. PMID: 25368619; PMCID: PMC4202688.
Aalberse RC, Stapel SO, Schuurman J, Rispens T. Immunoglobulin G4: an odd antibody. Clin Exp Allergy. 2009 Apr;39(4):469-77. doi: 10.1111/j.1365-2222.2009.03207.x. Epub 2009 Feb 13. PMID: 19222496.

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