The advent of the Omicron variant last November has alarmed experts as its genome shows many mutations – more than 30 – in the region that encodes the virus’s protein. This region of the virus is used in vaccines against COVID-19, which means that the effectiveness of antibodies that have been developed after vaccination or even after infection with previous variants of the virus may be reduced.
Researchers in the field of immunology have studied previous variants of the virus and found that, although emerging variants of the coronavirus were relatively resistant to antibodies, another arm of the immune system – mediated by specialized cells called T cells – could be called T cells. the new variants. but the Omicron had mutated more than any other variant they had studied before. Thus it is crucial to understand how these mutations could affect immunity after vaccination as well as previous infection.
The Professors of the Medical School of the National and Kapodistrian University of Athens, Efstathios Kastritis and Thanos Dimopoulos (Rector of EKPA) summarize data coming from a few but specialized and experienced laboratories around the world and converge to about the same conclusion: the new variants, including Omicron, remain sensitive to T-cell responses.
Antibodies are the focus of attention for assessing immunity to SARS-CoV-2. Researchers are monitoring the levels of antibodies, especially “neutralizing antibodies” that directly inhibit virus replication: a significant drop in neutralizing antibody levels is associated with an increased risk of symptomatic infection. Antibodies are easier to study compared to studying the response of specific T lymphocytes. Thus monitoring the antibodies that develop, their levels and their neutralizing ability, makes it easier to analyze them on a large scale as in the clinical studies of vaccines.
However, the advent of coronavirus variants has shown that antibody-based immunity can be relatively fragile and unstable to a rapidly changing virus. The neutralizing antibodies bind to a relatively limited region of the SARS-CoV-2 spike protein, which is used as the standard for designing multiple vaccines for COVID-19. Mutations at these sites may result in a weakening of protection against these antibodies.
Photo of T lymphocytes with scanning electron microscope
However, T-lymphocytes are more “resistant” to such variants of the virus. These cells perform a variety of immune functions, including acting as “killer” cells that destroy virus-infected cells. By killing infected cells, T lymphocytes can reduce the spread of the infection and possibly reduce the chance of serious disease.
Specific T-cell levels do not weaken as rapidly as antibodies, either after infection or after vaccination. And because T-lymphocytes can recognize far more sites along the spike protein than antibodies, they are able to recognize even variants of the virus. So far, analyzes at both the computer and lab models show that this is also true for the Omicron variant. Several research teams have cross-referenced the mutations in Omicron with sites in the SARS-CoV-2 genome that are known targets of T-lymphocytes and found that the majority of sites that recognize T-lymphocytes are in the Omicron.
Other studies analyzed T-lymphocytes obtained from individuals who had either been vaccinated for COVID-19 or had been infected with a previous variant of the virus and found that these T-lymphocytes could respond to Omicron. Therefore at the level of computer models and at the level of the laboratory the T-cell responses remain relatively intact but the question is what will happen in real life.
In general, T-cell responses have been associated with increased protection against severe COVID-19 in animal models and in human clinical trials. Researchers suspect that T-lymphocytes are responsible for the effectiveness of vaccines in preventing hospitalization due to Omicron infection. “Antibodies after all the vaccines showed reduced neutralizing ability against Omicron, and the researchers believe that the efficacy data we see in South Africa are most likely due to T-lymphocytes.”
In children between the ages of two and five, the Pfizer mRNA vaccine did not elicit an adequate response in terms of antibody levels, but the researchers did not examine the T-cell response. And the large, initial adult vaccine trials did not gather enough of the necessary samples to analyze whether T-cell responses could be correlated with vaccination efficacy. This is because studying the T-cell response is particularly difficult, complex and time consuming (eg it requires the study of the response of living cells). Possibly, newer, easier methods for studying T-lymphocytes will make the assessment of the T-cell immune response easier and feasible on a large scale. The T-cell response may also receive more attention as more variants of the virus appear and as people begin to shift their focus from the number of infections to the severity of the disease: if infectivity is concerned, then antibodies may be the more important measurement but if you focus on the serious disease – as the situation seems to be evolving for COVID-19 today – T-lymphocytes become much more important.
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