A body without an antibody
Russian scientists investigated the features of cellular immunity to coronavirus
Maria Nedyuk, Izvestia
It turned out that this protective mechanism can work both for those who have had COVID-19, and for those who have not encountered infection. It is likely that some of these subjects still suffered from the disease asymptomatically or their T-cell memory for other seasonal coronaviruses worked, experts suggest. Also, scientists were able to identify those areas of spike protein to which the body's defense system reacts the most. This will make it possible to create effective vaccines and accurate diagnostic test systems.
Not just antibodies
Most of those who have had COVID-19 have antibodies to the virus. But in some patients, this immune reaction is completely absent. The destruction of the virus in their body could occur at the expense of another part of the immune system – T-lymphocytes, or T-cells. In the majority of infected people, these cells are really able to recognize fragments of the virus, a study by scientists from the FSBI "NMIC Hematology" of the Ministry of Health of Russia showed. Moreover, it turned out that people who have not had COVID-19 also have T cells that respond to SARS-CoV-2.
In their study, the scientists described two types of immune response to the new coronavirus: antibodies and a T-cell response. They examined biomaterials of COVID-19 patients (31 samples) who were not ill (14), as well as samples from the biobank that were taken before the pandemic (10). It turned out that in the blood taken in the spring of 2020, those who have not suffered COVID-19 have significantly more T-cells that recognize the virus than in samples from the biobank. The authors of the study explain it this way: among those who did not get sick, some probably still managed to encounter the virus.
– We do not fully understand the nature of this immune response, – Alina Shomuradova, the first author of the article, a participant in the RNF grants, an employee of the National Medical Research Center of Hematology, told Izvestia. – A T-cell response can be observed due to the fact that immunological memory cells are activated for other coronaviruses that existed around us before 2019. Or, for example, these people actually suffered from COVID-19 asymptomatically and did not develop antibodies to the virus.
At the same time, those who had a negative result of the PCR test were considered not ill at work, the researchers stressed. That is, it cannot be ruled out that in fact the number of people who have been ill may be significantly higher than official data.
Special areas
Immunologists of the Hematology Center also described the areas of the spike protein SARS-CoV-2, which cause the strongest immune response in patients with COVID-19. Having met with this protein, the human defense system "remembers" the virus, and if it gets into the body, it will be able to neutralize it.
It turned out that two sections of the virus are recognized by the immune system of most people-carriers of the most common variant of the HLA-A gene in Europe, which is responsible for demonstrating fragments of viruses to T-lymphocytes. Both identified fragments are unique to the new SARS-CoV-2, that is, they distinguish it from other coronaviruses. This means that they can be used to identify people who have been ill with COVID-19.
– It should be understood that T-lymphocytes do not recognize the virus as a whole, but its short fragments. And different people have different fragments due to genetic characteristics," Grigory Efimov, head of the Laboratory of transplantation Immunology at the NMIC of Hematology of the Ministry of Health of Russia, told Izvestia. – It turns out that it is not so easy for the virus to escape from the immune system, because it could introduce mutations into recognizable areas and thereby become invisible to T-lymphocytes. But this is difficult, since such mutations will be effective against one person, but not for others.
Understanding exactly which fragments of the virus are recognized by the immunity of most people will help determine how effective the vaccines are and whether they contain these unique areas. It will also make it possible to create the most effective test systems that will show the level of T-lymphocytes, and indicate exactly SARS-CoV-2, and not any other coronavirus.
Effective vaccines
Some modern vaccines are designed not only for the production of antibodies, but also for the formation of cellular immunity, said Albert Rizvanov, director of the Scientific and Clinical Center for Precision and Regenerative Medicine at the Institute of Fundamental Medicine and Biology of KFU. From this point of view, the achievements of colleagues are important not only from the point of view of understanding fundamental processes, but also have practical significance.
– The Sputnik-V vaccine, as well as Pfizer and Moderna vaccines should work well not only to obtain antibodies, but also to stimulate cellular immunity, the scientist said. - They lead to the fact that the cells themselves begin to produce viral proteins-antigens and provoke a reaction to the antigen that would occur with a natural infection. This usually does not happen when using, for example, weakened recombinant or inactivated viral vaccines.
The findings of the study confirm the hypotheses about a fairly large number of people who do not have antibodies to SARS-CoV-2, but have T-cell immunity, said Pavel Volchkov, head of the laboratory of genomic engineering at MIPT (a university participating in the project to increase the competitiveness of education "5-100").
– Unfortunately, the sample in this work is so small that it does not give us the opportunity to draw conclusions about what percentage in our society is already protected in this way from COVID-19, – he noted.
According to the expert, if the analysis for T-cell immunity confirms its presence, then, from the point of view of immunology, it should protect a person at the next meeting with the coronavirus. But this fact also still needs to be proved.
– If I were the author of this article, I would form a large pool of such people with T-cell immunity, whom I would observe for a long time. Firstly, I wonder if they will get sick with COVID-19 or not. And secondly, I would try to keep track of how many T-clones they will have in the bloodstream after a while," Pavel Volchkov said.
The results of the work supported by the Russian Science Foundation (RNF) are published in the journal Immunity (Shomuradova et al., SARS-CoV-2 epitopes are recognized by a public and diverse repertoire of human T cell receptors).
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