The immune system versus the virus: Why Omicron worried experts from the start

Zoom / Illustration of antibodies that respond to SARS-CoV-2 infection.

Getty Images / Katrina Kohn / Science Photo Library

Since the first description of Omicron, researchers have been concerned about the type of SARS-CoV-2 virus. By looking at the list of mutations it carries, scientists can identify a number likely to make the variant more contagious. Other mutations were more worrying, as they likely interfered with the immune system’s ability to recognize the virus, allowing it to pose a risk to those who had been vaccinated or had a previous infection.

The underlying reason for these buried fears was obvious: Scientists could simply look at the amino acid sequence in the coronavirus spike protein and see how well the immune system would respond to it.

This knowledge is based on years of studying how the immune system works, along with a lot of specific information regarding its interactions with SARS-CoV-2. Below is a description of these interactions, along with their implications for viral evolution and current and future variants.

Ts and BS

To understand the function of the immune system, it is easiest to divide its responses into categories. First of all, there is the innate immune response, which tends to recognize the general features of pathogens rather than the specific characteristics of individual bacteria or viruses. The innate response is not regulated by vaccination or prior exposure to the virus, so it is not really relevant to discussing variants.

What interests us is the adaptive immune response, which recognizes certain traits in pathogens and generates a memory that produces a rapid and powerful response if the same pathogen is seen again. It is the adaptive immune response that we stimulate with vaccines.

The adaptive response can also be divided into categories. With regard to relevant immune responses, we are most interested in those that are mediated by antibody-producing B cells. The other major part of adaptive immunity, the T cell, uses an entirely different mechanism to identify pathogens. We don’t know much about the T-cell response to SARS-CoV-2, but we’ll come back to that later. For now, we’ll focus on antibodies.

Antibodies are large aggregates (molecularly speaking) of four proteins. Most proteins are similar across all antibodies, allowing immune cells to react to them. But each of the four proteins has a variable region that differs in each producing B cell. Many of the changed areas are useless, others recognize the proteins of the body and are eliminated. But by chance, some antibodies have variable regions that recognize a portion of the protein made by the pathogen.

antibody molecule.  The variable regions in the red and blue parts of the molecule combine to form a binding region that can recognize pathogens.
Zoom / antibody molecule. The variable regions in the red and blue parts of the molecule combine to form a binding region that can recognize pathogens.

The part of the pathogen protein that the antibody recognizes is called the epitope. Epitopes differ from protein to protein, but they share some features. It has to be on the outside of the protein, rather than buried inside, for the antibody to hit it in the first place. They often contain polar amino acids or have a charge, as these form stronger interactions with the antibody.

You cannot simply look at the amino acids in the antibody and decide what it will stick to. But if you have sufficient amounts of a particular antibody, it is possible to do what’s called “epitope mapping,” which involves figuring out where the antibody attaches to the protein. In some cases, this can include an accurate list of amino acids that the antibody recognizes.

In general, the presence of pathogen-bound antibodies in the bloodstream makes the pathogen easier to detect and eliminate by specialized immune cells – for this function, it doesn’t really matter where the antibody sticks. But there are also specific interactions that can inactivate the virus in some cases, as we will see below.

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