As the pandemic progresses, the variants of the virus follow one another in such a way that the one that gains contagious capacity prevails over the others. It is a common biological process in the relationship between pathogens and new hosts.
All viruses use the cells of their hosts to proliferate. To do this, they introduce their genome into the cell and hijack the machinery to replicate their genome and make their proteins. Then, they assemble the genome within an external structure and thus form new viruses that escape the cells virtually exploding them. This is how they damage tissues.
The key and the door, keys to infection
Viruses use different strategies to introduce their genome into cells. In the case of SARS-CoV-2, one of the proteins involved is protein S or Spike, which has been chosen for immunization by vaccines. The virus’s protein S must bind to the cells’ ACE2 protein in order for the virus to enter its genome and force the cell to make more viruses.
Protein S would be like the key to lock the door of cells, a role that the ACE2 protein would play. The better the key is in the lock, the easier it is for the virus to infect, and it will do so faster and more efficiently. Thus, the variants that are imposed are those that improve their ability to bind to the ACE2 protein and are thus more contagious.
Can there be infinite variations?
At this point in the pandemic, and perhaps before, there will have been thousands of mutations that have resulted in variants that have not been successful and others that have been imposed, such as delta in Europe or lambda in South America, almost all with mutations in protein S.
All parts of protein S are important, but two of them are the ones that gather the most interest: the area of binding to the ACE2 protein or RBD area and the area where its synthesis begins or NTD area. The immune system response focuses especially on the RBD and NTD areas to produce what are known as neutralizing antibodies, those antibodies that prevent the binding between the virus and the cell. The lambda variant has mutations in both areas. One of them is an insertion in the NTD region considered important to evade the immune system.
However, the mutations in the variants cannot be infinite. Once protein S is highly efficient in binding to human ACE2 protein, it cannot change much anymore. Any change in the teeth of the key would impair the attachment to the lock and therefore the ability to infect cells.
The immune system recognizes the virus by different mechanisms.
Before the appearance of any new variant, studies are generated that determine if the antibodies of patients who have already passed COVID-19 or of vaccinated people can block it or not. In general, it always focuses on the presence of neutralizing antibodies and the activity of cytotoxic (Tc) and helper (Th) T lymphocytes continues to be underestimated.
T lymphocytes recognize small pieces of proteins (peptides) from the proteins of viruses that invade cells (Tc) or from those that have been digested by cells specialized in presenting antigens (Th).
For T lymphocytes to recognize these peptides, all cells in the body express specific proteins called major histocompatibility complex (MHC). All cells present six different proteins of this complex and antigen-presenting cells six more.
The MHCs select the peptides and display them to the lymphocytes as a control of what the cells are producing or have eaten. If a cell is infected or has engulfed a virus, it will present peptides from it in its MHCs. They can already understand that cells present a very high collection of these peptides that do not have to belong to protein S. In fact, in patients recovered from COVID-19, up to 41 different peptides have been identified that develop a strong immunological memory in the T lymphocytes, 18 of them from protein S.
The activation of T lymphocytes also generates a signaling protein called interferon whose function is to inhibit the synthesis of proteins and RNA in the cells it affects and, therefore, slow down the proliferation of viruses. Therefore, the activation of T lymphocytes would explain the resistance of certain patients to developing the disease during the onset of the pandemic by presenting a strong immune memory against peptides common to almost all beta coronaviruses, including humans.
Do variants of the immune system escape?
Recently an article, not yet published or peer reviewed, has shown the characteristics of the lambda variant. However, this article also bases its conclusions on the presence of neutralizing antibodies and not on the general immune response.
Practically all the variants have been spoken of “evading immunity”. About the delta variant was also indicated. But, in his case, of 34 antibodies with neutralizing capacity, only 14 of them lost their function. The remaining 20 maintained it and the activity of T lymphocytes was not determined.
The truth is that even in the face of the aggressive delta variant and the release of mobility in the UK, vaccines have shown great ability to prevent disease and virus transmission. It is enough to pay attention to the contagion curve, bed occupancy and deaths that occurred in the United Kingdom, Israel or Spain, all of them countries with a high vaccination rate.
Taking into account the generation of immunological memory and the variability of virus structures recognizable as antigens by B and T lymphocytes, it is not expected that the new variants can effectively “evade” the entire immune system. The following infections in vaccinated people, which cause at most mild symptoms with the new variants, will strengthen the immune response against the new variants. 
Guillermo López Lluch, Professor of the Cell Biology area. Associate researcher at the Andalusian Center for Developmental Biology. Researcher in metabolism, aging and immune and antioxidant systems, Pablo de Olavide University
This article was originally published on The Conversation. Read the original.
