Berlin, 11 October 2023
One vaccination in the upper arm – and the whole body is protected. How does that work? For one thing, the immune system produces antibodies and cells that patrol the entire organism in the blood. On the other hand, as a recent study by the Charité – Universitätsmedizin Berlin shows using the example of corona mRNA vaccines, the body builds up a local immune memory in various organs. According to the work published in the Journal of Clinical Investigation*, the immune memory cells are more numerous in the organs than in the blood and have enhanced antiviral defence functions.
The researchers had suspected it: findings from the animal model have indicated for some time that most cells of the immune memory do not circulate in the blood after an infection, but become resident in the organs and protect them locally. It is assumed that this also happens after vaccination. However, proving this in humans is not trivial. “For this, you need tissue from many people with a known and comparable vaccination history, who have preferably never been infected by the pathogen,” explains Prof. Dr. Katja Kotsch, head of the study from the Clinic for General and Visceral Surgery at the Charité. The Corona pandemic with its many vaccinations now made it possible to obtain the necessary samples.
Memory cells in liver, kidney and lung
For the study, the researchers examined tissue from different organs that was obtained during medically necessary operations, for example to remove a tumour. The samples came from 61 people who had been vaccinated against the coronavirus two to three times with an mRNA vaccine a few months before the operation, regardless of the operation, but most of whom had not yet undergone the infection.
Through specific stimulation and staining of immune cells, the research team succeeded in detecting so-called CD4-positive T-helper cells in several tissues, which were directed against SARS-CoV-2. These immune memory cells ensure that other immune cells produce suitable antibodies against the pathogen as soon as it is detected in the body. They also presumably contribute to fighting the virus directly.
The scientists found the immune memory cells not only in the spleen and bone marrow, tissues where immune cells mature or are produced by default, but also in the liver, kidney and lung. “These data confirm our assumption that after a vaccination, the body creates an immune memory that is stable over months, even in tissues that are far away from the injection site,” says Dr. Arne Sattler, immunologist in Prof. Kotsch’s team. Together with her, he is the corresponding author of the study. “We have now shown this for the mRNA vaccines against coronavirus, but we assume that similar processes also take place after other vaccinations. However, the evidence for this is still lacking and further studies are needed.”
Organ immune memory is created largely independent of age
A comparison with blood samples from the patients showed that there were significantly more immune memory cells in the kidneys, liver and lungs than patrolled the blood. The messenger substances secreted by the cells in the organs also indicated particularly pronounced antiviral properties. Dr. Sattler sums up: “Our data show that the immune memory in the organs is functionally superior to that in the blood. What this means exactly for the immune protection of the organs is not easy to deduce, because the exact protective effect of individual immune cells in humans cannot be determined well. However, observations in animal models suggest that such locally anchored, potent T cells are better able to ward off pathogens.”
And another difference was shown between the immune memory in the organs and the blood: the number of protective immune cells that settled in the organs was similar regardless of the age of the vaccinated person. In contrast, fewer immune memory cells circulated in the blood of older people than in younger patients. “In other words, after the Corona vaccination, the body stores a similar number of immune memory cells in the organs of old people as it does in young people,” says Prof. Kotsch. “According to our data, the organ-specific memory cells last at least a few months. Whether the immune memory even remains stable in the tissue for years is the subject of further investigations.”
*Proß V, Sattler A, Lukassen S et al. SARS-CoV2 mRNA-vaccination-induced immunological memory in human non-lymphoid and lymphoid tissues. JCI 2023 Oct 10. doi: 10.1172/JCI171797
About the study
Under the leadership of Prof. Dr. Katja Kotsch, head of the Experimental Tumour and Transplantation Immunology Unit, the work was carried out in close cooperation with the Berlin Institute of Health at the Charité (BIH, Dr. Sören Lukassen and Prof. Dr. Christian Conrad). Vanessa Proß is an equal first author of the study alongside Dr. Lukassen and Dr. Sattler. The research was mainly funded by the German Research Foundation (DFG).
Image: A so-called flow cytometer (left) allowed the researchers to detect the immune memory cells © Charité | Arne Sattler