Can the Omicron variant escape the immune system?

A new variant of the coronavirus baptized as omicron has come to disturb the end-of-year plans especially in Western countries, although concern about an escalation of infections already existed in those European countries with low vaccination rates in which the collapse of health services was beginning to be a reality .

Faced with the announcement of this new variant, the governments of many countries have once again announced mobility restrictions. But is it really as worrying as it sounds? Can it be more contagious and dangerous than the previous ones?

The data we have tells us possibly not. In South Africa, a country where the new variant is discovered thanks to the fact that they have a good tracking system, there has not been an upturn in cases or deaths that could suggest a greater severity. In fact, even the reported cases do not show an aggressiveness different from that of other variants such as delta, predominant in Europe.

What do we know about this new variant?

The only thing we know is that it is already in different countries of the planet and that its most relevant characteristic is that contains 32 mutations in protein S compared to the original virus that was sequenced in Wuhan. Some of these mutations were already in the previous variants of concern. These mutations gave the virus a greater affinity for the receptor, which we already knew was going to happen.

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However, that is not to say that these mutations make vaccines less effective. Nor is it that the immune system is unable to recognize the S protein of this new variant.

Protein S is a glycoprotein and that matters

The most efficient vaccines against SARS-CoV-2 are vaccines based on messenger RNA (mRNA). These vaccines cause the cells that receive the vaccine to make a piece of protein S in the same way that they would if the virus had infected them.

Protein S is a glycoprotein, that is, some of its amino acids have sugars attached. It is as if it were glazed, covered with different types of sugars that form long chains. These sugars bind to the protein by two mechanisms: by the union of a complex of 14 sugars to some amino acids asparagine or by means of the union of sugars to the amino acids serine, threonine or tyrosine.

Well, sugars are important for the interaction with antibodies, since they can be recognized by them or mask antigens that would only be recognizable by removing sugars. Interestingly, already in the AIDS virus it was shown that sugars bound to the membrane glycoprotein bound to antibodies with a potent ability to neutralize the virus in some of the patients.

Of the 32 mutations that omicron contains in protein S, eight of them affect a possible glycosylation site. Two of them create possible new sites while six of the previous asparagine disappear. They all occur due to a specific mutation.

Nevertheless, of the 22 amino acids that could be glycosylated in protein S, none have changed so far. The glycosylation pattern of protein S has not undergone modifications since the original protein. This is so since the stability of the glycosylation sites is essential for the interaction of the virus with the cells to be infected.

In fact, this pattern is highly conserved among coronaviruses, possibly because if it changed it would seriously affect the infective capacity of the virus.

For all this, it is very possible that many of the mutations detected in omicron do not produce noticeable differences in the antibody-dependent immune response generated by vaccines.

Why is the role of T lymphocytes always neglected?

Another aspect that seems to be forgotten is that the immune response does not only depend on antibodies. We must add the essential role of T lymphocytes. T lymphocytes do not recognize protein S in its natural, folded form with sugars attached. What they do identify are the small chains of amino acids in the protein that have been chopped up and presented in the cells attached to what we know as histocompatibility complexes.

In the case of SARS-CoV-2, the protein S produced by vaccines contains amino acid sequences that are recognized by the histocompatibility complexes of almost 100% of the population and that they have not undergone mutations, possibly because they are sequences that are very necessary for the function of the protein. Therefore, we should also not expect the T cell response to be severely affected by mutations, as has already been demonstrated with the previous variants.

The evolutionary conservation of these sequences has already allowed many people to have passed the contagion asymptomatically, since they showed an immune response against SARS-CoV-2 simply by having had Previous contact with human coronaviruses that present sequences common to all coronaviruses.

A functional system cannot undergo drastic changes

Evolutionarily speaking, we should no longer expect large changes in protein S. Most of the changes produced in a system that is already functional makes that system less effective. In the case of the coronavirus, mutations that produce important structural changes in protein S would interfere with its function. In short, no major changes are expected that significantly increase the effectiveness of a virus that is already, in itself, very efficient at spreading.

All the political, economic and media noise of these days responds more to a kind of pandemic panic than to science. You have to analyze, check and be calm to take effective measures. And the most efficient of the measures is for the largest number of people around the world to be vaccinated so that their immune system prevents them from suffering from a COVID-19 with serious symptoms.

Guillermo López Lluch, Professor of the Cell Biology area. Associate researcher at the Andalusian Center for Developmental Biology. Researcher in metabolism, aging and immune systems and antioxidants., Pablo de Olavide University

This article was originally published on The Conversation. read the original.