There is remarkable news regarding the immune response to SARS-CoV-2. It is clear now that the virus mutates to evade the neutralizing antibody responses. There are new results that suggest that is not the whole story. When it comes to another arm of immunity, T-cell immunity, high response to one form of the virus means high response to them all. Here we will review what that might mean for the future of Covid-19.
In the months since SARS-CoV-2 variants came to the forefront of Covid-19 discussion, the average person is left with a number of questions. Will the vaccine my grandmother just received protect her from emerging strains? What about my previous infection during the summer? How long might that protection last?
Vaccines and prior infections confer antibodies, which are proteins produced by B-cells to counteract a specific antigen. Picture a custom couture tailored to you. The fabric aligns perfectly with every inch of your torso. An antibody is like a tailor-made protein that fits a specific pathogen, in this case, SARS-CoV-2. However, ample research indicates that these antibodies fade rather quickly over time, and may not protect as well against some variants. Though as it turns out, B-cells and antibodies are only half the adaptive immunity puzzle.
The other piece is the T-cell. These are types of white blood cells in the immune system which act as the front-line soldiers against disease. Their purpose is to eliminate invading pathogens and clean up dead cellular debris. They do this by remembering past infections, waiting to encounter short amino acid sequences of the virus called peptides, then killing the virus when it reappears. Whereas antibodies are tailor-made proteins for a specific virus, T-cells attack a range of different pathogens, like a suit purchased off the rack. It may not quite fit exactly, but close enough will do and it will fit many others as well.
The T-cell is another tool in the arsenal against Covid-19, but the questions above must be translated in reference to this secondary weapon. Will T-cells protect against rapidly emerging variants of the virus that show signs of resistance to antibodies? Research from the La Jolla Institute of Immunology, led by Dr. Alessandro Sette and Dr. Shane Crotty, sought to illuminate these unknowns.
Their findings were encouraging. When exposing human T-cells from a wide range of hosts previously infected with Covid-19 to a number of SARS-CoV-2 variants, the T-cell response held up well. Responses decreased at most 30% relative to that cell’s response to the SARS-CoV-2 wild type. In some cases, such as the South Africa variant, T-cells produced a nearly equal response to the variant as the unmutated virus.
The same can be said for samples pulled from people vaccinated against Covid-19. Their T-cells responded in an equal or slightly decreased volume in comparison to the wild type. This is a major victory, confirming that T-cells have some effect in slowing mutated variants down, but to what extent?
There are strengths and weaknesses to the T-cell response. The strength, as shown by these researchers, is the blanket coverage they have over the variants. The virus is adaptive and mutative—changing over time. When we introduce antibodies specific to the virus, it has shown an ability to develop mutations to the receptor-binding domain, n-terminal domain, or elsewhere, that renders the antibody less effective. With T-cells, because everyone has their own unique hereditary set rather than one specific developed antibody from a vaccine or previous infection, the virus cannot adapt.
The weakness, however, is that T-cell responses to SARS-CoV-2 are limited. T-cells are not designed to prevent infection, only to kill the cells once they are in the body. The researchers confirm this by concluding that “while it is not anticipated that circulating memory T cells would be effective in preventing SARS-CoV-2 infection, it is plausible that they can reduce Covid-19 severity.”
Given all this, it may be the case that SARS-CoV-2 is allowing a certain level of T-cell response. Variants evolved while T-cells were present, prompting the idea that viruses are modulating the T-cell response to low enough levels for them to continue to spread. While mostly speculative, it seems possible that the virus could have regulatory influence on the T-cell.
Regardless, T-cell reactivity in the face of variant forms of SARS-CoV-2 is an unmitigated positive. The implication is that those vaccinated or previously infected will have at least some form of defense against newly circulating variants, even if they are capable of evading antibodies. This is much needed positive news in the face of the growing variant threat.
