Another Study Confirms the Rise of IgG4 after the mRNA shots

This article presents another study showing that the immune-tolerant IgG4 rises after COVID-29 mRNA injections.

The International Society for Infectious Diseases published The Appearance of Anti-spike Receptor Binding Domain Immunoglobulin G4 Responses after Repetitive Immunization with Messenger RNA-based COVID-19 Vaccines in November 2023.

The authors are from the Department of Microbiology & Immunology of the Fukuoka University in Japan.

Background

The idea behind the mRNA vaccinations for COVID-19 is to elicit antibodies against the SARS-CoV-2 that will confer long-lasting immunity. For that, we need antibodies or immunoglobulins, aka IgG.

But there are different kinds of IgGs: IgG1, IgG2, IgG3 and IgG4. To protect against viruses, we need IgG1 and IgG3 because they work with other immune cells to cause inflammation and eliminate the invaders.

High levels of IgG2 and IgG4 do not cause inflammation and do not protect. Both are considered to be immune-tolerant IgGs.

Immune-tolerant IgG2 and IgG4 have Uses

People with severe life-threatening allergic reactions, such as bee stings, get allergy shots after small amounts of bee venom are injected into the skin for several weeks. This results in the slow rise of IgG2 and IgG4.

Both IgG2 and IgG4 modulate the allergic response. That way, if the person gets stung by a bee again, the allergic response will not be as life-threatening.

That’s well and good for allergies, but you don’t want an immune tolerance against a viral infection, or a mild illness can become severe or deadly.

In the study, the Japanese researchers found that repeated mRNA COVID vaccines increased the IgG4 antibody.[1]

One month after the second dose, the IgG4 increased by 6.76%. Six months after the second dose, it went up by 50.5%. And one month after the third dose, it reached 97.2%.

The graphs below show the progressive rise in IgG4, as shown by the black dots from the first to the third dose.

In contrast, repeated COVID booster shots decreased the IgG3 produced.

The decreasing IgG3 can be seen in the graphs below.

Also, the IgG4 continued to increase after breakthrough infections in those who received the COVID shots.

Not only did the IgG3 decrease but so did its partner in protecting against infection, the IgG1.

The other immune-tolerant IgG2 was also increased after the third and fourth mRNA shot.

Natural Immune Response Does not Increase IgG4

The study also found that those who were unvaccinated with the COVID-19 shots but were previously infected with COVID-19 did not develop a rise in the IgG2 and IgG4.

Natural immunity developed from COVID-19 does not increase tolerance for SARS-CoV-2 as nature intended.

But what about those who recovered from COVID-19 and then got the mRNA shots? Did their IgG4 increase?

The answer is yes. Kiszel and colleagues concluded this in their study: Class switch towards spike protein-specific IgG4 antibodies after SARS-CoV-2 mRNA vaccination depends on prior infection history published by Scientific Reports in August 2023.

Did the elevated levels of IgG4 change the immune response to breakthrough COVID-19?

In their study that lasted for 15 months, they found that,

In our cohort, we did not find any evidence to suggest that the increased anti-RBD IgG4 Ab levels observed after repeated mRNA-based COVID-19 vaccination increased the risk of breakthrough infection.[1]

However, the healthcare workers are relatively young Japanese and have normal body mass index, meaning they were neither overweight nor obese. They recognize this and mention it in the limitations of their study.

Finally, since our cohort was mainly composed of healthy individuals under 65 years of age, the result of the study cannot be applied to a population that includes older individuals or those with underlying diseases that may cause immunodeficiency.[1]

In previous studies, high levels of IgG4 have resulted in worse COVID-10 outcomes. I wrote about it in Three Studies Link High IgG4 to Severe COVID-19.

Cancer and autoimmune diseases are also related to high IgG4 –

The rise of IgG4 in this study from Japan aligns with other research about the Pfizer and Moderna mRNA shots.

Could the rise in IgG4 explain why COVID-19 continues to persist, as headlined by the CDC?