Bone marrow cells drive vaccine effectiveness

Platelet precursor cells, when active, increase the resistance of antibody-producing cells, enhancing the immune response to the vaccine.

Different vaccines work differently. For example, the MMR vaccine against measles, mumps and rubella is vaccinated in childhood and is never remembered again, while the flu vaccine has to be updated every year. Naturally, a lot depends on the pathogen against which the vaccine is made; and in the case of influenza, the problem is that the virus itself is regularly “updated”; new strains appear that the immune system does not sense, having been trained by the vaccine on the strains of the previous version. But it happens that the same vaccine against the same virus works with different effectiveness in different people. After the vaccine, the level of antibodies against a specific pathogen increases in the blood – this means that the immune system has understood the threat and has cells that synthesize the necessary antibodies. Then their level decreases, but after, for example, a month, one person still has these antibodies, while another turns out to have so few that we can assume that they don’t exist.

Megakaryocyte (left) and platelet. (Photo: SNSF Scientific Image Competition / Flickr.com)

To understand what could be the matter, employees Stanford Universityconducted an experiment with fifty volunteers who were injected with the H5N1 bird flu vaccine (the vaccination was done twice and in some cases with an adjuvant, that is, a special “additive” that enhances the immune response, and in some cases without an adjuvant). Then, over the next hundred days, the participants in the experiment had their blood taken for analysis more than ten times: the amount of antibodies and many other proteins in the samples was measured, as well as the activity of genes in the blood cells. The result was a large array of data, which was given to artificial intelligence – the algorithm had to find patterns between different parameters. A pattern was found: in those whose immunity responded well to the vaccine, and whose level of antibodies against the virus remained quite high after a month, special pieces of RNA from activated megakaryocytes were found in their platelets.

Platelets are known to be needed in blood clotting reactions. You can’t call them cells – they’re just pieces of cytoplasm, detached from those same megakaryocytes, very large cells sitting in the bone marrow. Platelets are released from them as needed, and in order for the megakaryocyte to begin producing platelets, it must be activated. At the same time, the activity of genes in it changes, which is noticeable in the different RNAs into which information from DNA is translated. RNAs synthesized in the megakaryocyte nucleus are released into the cytoplasm, but platelets are, in fact, pieces of the cytoplasm of megakaryocytes, and these RNAs can be detected in them. In an article in Nature Immunology states that the effectiveness of the vaccine can be predicted by the amount of RNA residues in blood platelets taken a week after vaccination: the more megakaryocyte RNA, the stronger the vaccine’s effect. Experiments with mice confirmed this pattern: the mice were also given the bird flu vaccine, but some were also given thrombopoietin, a protein that stimulates the growth and development of megakaryocytes. With thrombopoietin, the level of antiviral antibodies in mice after two months was six times higher than in mice that were not given thrombopoietin.

Later it turned out that active megakaryocytes interact with plasma cells – B-lymphocytes, which began to produce antibodies. Interaction with megakaryocytes makes plasma cells more resistant to various stresses, increasing their survival. The same thing is happening with other vaccines: Researchers assessed the immune response in nearly two and a half hundred people vaccinated with seven different vaccines, including Covid and yellow fever, and in each case the RNA in the platelets indicated a strong immune response. Perhaps here it will be possible to create a clinical method of analysis that will help in routine medical practice to determine how the vaccine worked and whether an additional portion of it is needed. In the future, you can think about enhancing the effect of the vaccine in advance by specifically stimulating megakaryocytes – but only in such a way that this stimulation does not harm anything.

Source: www.nkj.ru