Five years after the introduction of the first mRNA corona vaccines, scientists are gaining clarity about the most important side effect that occurred when these vaccines were administered. Fewer than one in 10,000 vaccinated people, mostly young men, developed myocarditis, or inflammation of the heart muscle, shortly after the injection.
American researchers from Stanford and Harvard universities have unraveled that the cause of this rare side effect lies in an interplay between macrophages and T cells that respond to foreign genetic material in the body. In the article about that, she wrote on Wednesday publish in Science Translational Medicinethey also immediately present a drug that can dampen the unwanted reaction: the phytoestrogen genistein.
During the corona pandemic, vaccines based on the new principle of a piece of messenger RNA were introduced on a large scale for the first time. This is a piece of synthetic genetic material that contains the instructions for the production of the so-called spike protein, which is also on the outside of the SARS-CoV-2 coronavirus. The body cells of the vaccinated person are stimulated to produce this spike protein, which causes the immune system to recognize it and produce protective antibodies against the virus. The mRNA vaccines from Pfizer and Moderna, which have also been used in the Netherlands, have proven to be safe vaccines that prevented people from becoming seriously ill or dying from Covid.
After the population-wide vaccination campaigns during the corona pandemic in 2021, there were also vaccination campaigns in the Netherlands several hundred reports of myocarditis within at the Lareb side effects center. People affected had complaints such as shortness of breath, fever, chest pain and palpitations. In most cases, these complaints were transient, and moreover, the risk of this complication was much greater in people who had not (yet) been vaccinated and contracted Covid. After all these reports, the side effect was officially added to the package leaflet of the vaccines, but what exactly caused the sudden inflammation of the heart muscle remained unclear.
Immune system alarms
The American researchers finally took a closer look at the mechanism. They used data from two previous studies on people who had received the Pfizer vaccine and whether or not they had developed symptoms. For example, the researchers came across two signaling substances that were increased in the blood of the participants after vaccination, especially in those with complaints. This involved the cytokines CXCL10 and interferon-gamma, both alarm substances of the immune system that trigger an inflammatory response.
With this knowledge, the authors shifted their research to experiments with cultured immune cells and mice. For example, they discovered in a culture dish that macrophages, a type of immune cell that is often the first to respond, will produce large amounts of CXCL10 in response to exposure to a dose of the mRNA vaccine. They then discovered that T cells, a type of white blood cell, responded to this signal by in turn producing large amounts of interferon-gamma.
Research with mice subsequently showed that vaccination could indeed cause heart inflammation as a side effect, but that the same effect could be achieved with the cocktail of the two alarm substances. If they blocked the action of CXCL10 or interferon-gamma with molecular inhibitors, the inflammation of the heart muscle was also much less.
One of the researchers on the team, Joseph Wu, had previously worked with the substance genistein, a phytoestrogen derived from soy. He showed at the time that this drug could limit blood vessel and heart damage due to excessive cannabis use, which was attributed to its anti-inflammatory effect. They also decided to test genistein in their side effect study, because it fits very well with the picture that there is also a hormonal effect in the side effect. Statistics show that young men in particular suffered from myocarditis after vaccination. In the subsequent experiments with mice, the substance was indeed found to be able to dampen heart inflammation after vaccination.
The authors write that their research is not only important for the Pfizer and Moderna corona vaccines, but for all (future) mRNA vaccines. After all, the piece of mRNA that is introduced could, in rare cases, provoke a transient inflammatory response with all these vaccines, in the heart but also in other organs.
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