Two peer-reviewed German studies, published three weeks apart, found that mRNA COVID-19 vaccines cause recipients to produce a type of antibody that is less effective against the virus over time. This type of antibody is classified as IgG4.
The first study, published in Science Immunology on Dec. 22 and titled, “Class Switch Toward Non-Inflammatory, Spike-Specific IgG4 Antibodies After Repeated SARS-CoV-2 mRNA Vaccination,” focused on mRNA boosters and showed how multiple mRNA shots negatively impact the immune system response.
The second study, published in Frontiers in Immunology on Jan. 12, confirms the findings and builds upon the research of the first, this time studying the two-dose primary series of both the Pfizer and Moderna COVID-19 mRNA shots.
Notably, the latest Frontiers study lists Shikha Shrivastava, a senior scientist at Pfizer, as editor and Lela Kardava, a staff scientist recently under the Anthony Fauci-directed National Institute of Allergy and Infectious Diseases (NIAID), as a peer reviewer.
Researchers first submitted the study for publication to Frontiers on Aug. 16, 2022. This fact, combined with the study’s editor coming from Pfizer and a peer-reviewer from NIAID, suggests that both the mRNA vaccine producer and the government were aware of the potential antibody problem around the time that the U.S. Food and Drug Administration (FDA) authorized both the Pfizer and Moderna Omicron bivalent boosters in late August.
The studies’ findings also come at a time when the government continues to push the bivalent boosters despite health experts’ admission that the latest COVID-19 variants, such as the quick-spreading XBB.1.5 variant, are evading vaccines.
Johns Hopkins Bloomberg School of Public Health published a report in early January that stated, “The XBB family of variants emerged a few months ago and caught virologists’ attention because it contains more mutations to evade immunity than any other variant.”
And the World Health Organization (WHO), in a report on Jan. 11, stated that the “XBB variants are the most antibody resistant variants to date … These data reported that sera from individuals with a) BA.1, b) BA.5, or c) BF.7 breakthrough infection and three doses of the inactivated vaccine (Coronavac), or d) BA.5 infection following three or four doses of mRNA vaccine (BNT162b2 or mRNA-1273) do not induce high neutralization titers against XBB.1.5.5.”
According to the latest Center for Disease Control and Prevention (CDC) numbers, XBB.1.5 accounts for 43 percent of all COVID-19 infections nationwide.
IgG4 Explained
According to livescience.com, antibodies “are specialized, Y-shaped proteins that bind like a lock-and-key to the body’s foreign invaders–whether they are viruses, bacteria, fungi or parasites. They are the ‘search’ battalion of the immune system’s search-and-destroy system, tasked with finding an enemy and marking it for destruction.”
The Cleveland Clinic explains that the body has five different types of antibodies. IgG is the most common, making up about 70 to 75 percent of all human antibodies, and contains four subclasses—gG1, IgG2, IgG3, and IgG4—each with different roles for immune response.
According to ScienceDirect, “In adults, IgG1 is the predominant subclass, accounting for approximately 70 percent of total IgG, and IgG2, IgG3, and IgG4 account for approximately 20%, 7%, and 3% of the total, respectively.”
Dr. Paul Alexander explained in his Substack that, in general, IgG4, with its “concentration of less than 5% of total IgG” antibodies, “plays a limited role in the immune process.”
In the Frontiers study, the authors explain that “IgG1 and IgG3 are the IgG subclasses with the highest potential to activate the immune system, whereas IgG4 has less activating potential and can even inhibit the effector functions of IgG1 and IgG3.”
William A. Haseltine explained in Forbes that “IgG1, IgG2, and IgG3 provide protection not only by blocking the virus from entering the cells but also by their … activiating effector functions and signaling the immune system to kill infected cells.”
“IgG4, however, does not activate the effector functions, meaning their presence may impact how the body responds to Covid-19,” he continued. “IgG4’s decreased effector functions could signal less robust neutralization and clearance of virus and infected cells.”
Frontiers Study Details
The Frontiers study researchers recruited 157 people and split them into six groups. Five of those groups had participants which had no known prior COVID-19 infection and were given either two doses of Pfizer, Moderna, or the non-mRNA AstraZeneca vaccine or one dose of AstraZeneca followed by one dose of either Pfizer or Moderna.
The sixth group contained participants who were previously infected but not hospitalized; they received one or two Pfizer doses.
The study found that “repeated immunization of [previously uninfected] individuals with the mRNA vaccines increased the proportion of the IgG4 subclass over time which might influence the long-term [antibody] effector functions” such as neutralization of the virus.
Regarding the study’s findings, Alexander wrote in his Substack that the “concern is that with potential class switching (due to repeat COVID injections/boosters) toward the IgG4 class (a non-inflammatory [antibody]), this can promote immune tolerance and as such a sub-optimal immune response.”
And HealthMatters explains that when testing bloodwork in a lab, “the presence of high serum IgG4 levels is considered a biomarker for IgG4-related diseases,” and “systemic inflammatory disease” is “characterized by an elevated serum IgG4 level.”
Alexander also wrote in his piece that the Frontiers study’s findings “mirrors or supports” the earlier-published Science Immunology study, which found a “potential immune tolerance (IgG4 switch) via class switch towards non-inflammatory, spike-specific IgG4 antibodies after repeated SARS-CoV-2 mRNA vaccination.”
“These two papers signal potential problems with immune tolerance increasing with repeated doses,” Alexander concluded.
Kilian Schober, co-author of the Science Immunology study, called his study’s findings of the immune system’s IgG4 dominance “very unusual.”
In a Twitter post, he explained, “shortly after 3rd vaccination, about 20% of IgG is IgG4, which is further boosted through breakthrough infections … to up to 40-80%. This is very unusual.”
Other Frontiers Study Findings
The Frontiers study researchers did not find a long-term LgG4 dominant response in those participants who received two doses of the non-mRNA AstraZeneca vaccine within the 270-day-long study.
However, they did find that of those who received an mRNA vaccine— whether they were in the groups that received the full mRNA primary series of two doses or the one that got only one dose following an initial AstraZeneca vaccine—”induced a long-term LgG4 response.” These findings suggest “that only mRNA vaccines generate detectable long-term LgG4 responses at least until day 270.”
Additionally, the Frontiers study researchers found that the participants who received the Moderna vaccine as their mRNA dose (regardless of whether they received it as a two-dose primary series or only once following the AstraZeneca dose) “showed a higher potential to generate … a late LgG4 response” than those who received any Pfizer dose. The researchers speculated that this finding was due to Moderna having “higher amounts of mRNA than the [Pfizer] vaccine.”
According to the researchers of the Science Immunology study, the long-term impact of the “class switch” to IgG4 antibodies is unclear but merits further examination.
Schober, in his Twitter post shortly after the Science Immunology study was published, said, “Given the enormous potential of mRNA vaccines for the fields of infectious diseases, autoimmunity, and cancer, the induction of IgG4 antibodies clearly requires further investigation. Deciphering the precise immunological mechanism underlying this class switch will be fun!”
