From the first description of Omicron, researchers have been concerned about a variant of SARS-CoV-2. By looking at the list of mutations it carries, scientists can identify some that likely make the variant more contagious. Other mutations were more concerning, as they likely interfered with the immune system’s ability to recognize the virus, putting it at risk for those who had been vaccinated or had a previous infection.
The underlying reason for these buried fears was clear: 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 study of how the immune system works, along with a lot of specific information about the interactions with SARS-CoV-2. Following 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 categorize the reactions. First of all, there is the innate immune response, which tends to recognize the general characteristics of pathogens rather than the specific characteristics of individual bacteria or viruses. The innate response is not regulated by vaccination or previous exposure to the virus, so it is not really relevant to discuss variants.
What interests us is the adaptive immune response, which recognizes certain traits of pathogens and generates a memory that produces a rapid and powerful response when the same pathogen is seen again. It’s the adaptive immune response that we elicit with vaccines.
The adaptive response can also be divided into categories. With regard to relevant immune responses, we are most interested in those mediated by antibody-producing B cells. The other major part of adaptive immunity, the T cell, uses a very different mechanism to identify pathogens. We don’t know much about the T-cell response to SARS-CoV-2, but we’ll get to that later. For now we will focus on antibodies.
Antibodies are large aggregates (molecularly speaking) of four proteins. Most proteins are similar for all antibodies, allowing immune cells to respond to them. But each of the four proteins has a variable region that differs in each producing B cell. Many of the altered areas are useless, others recognize the body’s proteins and are eliminated. But coincidentally, some antibodies have variable regions that recognize some of the protein made by the pathogen.
The part of the pathogenic protein that the antibody recognizes is called the epitope. Epitopes differ from protein to protein, but they share some characteristics. It has to be on the outside of the protein, rather than buried in it, 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 can’t just look at the amino acids in the antibody and decide where it sticks to. But if you have adequate amounts of a particular antibody, it’s possible to do what’s called “epitope mapping,” which involves figuring out where the antibody attaches to the protein. In some cases, this may contain 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.