A number of SARS-CoV-2 strains currently in circulation, as well as any future variants that may emerge, have the potential to evade the immune system’s cytotoxic T cell response in a subset of the general population.
According to Antonio Martin-Galiano of the Carlos III Health Institute in Spain and his colleagues, a new modeling study published on February 10th, 2022, in PLOS Computational Biology came to this conclusion.
Individuals differ in their HLA molecules, which are trained to recognize invading infections based on distinct components, or “epitopes,” of the pathogens. The T cell response in humans is genetically encoded by HLA molecules, which implies that different individuals have different HLA molecules.
Due to the large number of distinct HLA molecules found in the human population, as well as the large number of potential epitopes found in any particular virus, it is not practical to conduct an experimental evaluation of the immune response of each human HLA allele to each viral variation.
But computational methods can make this process a lot easier to complete.
According to the latest paper, the researchers first determined the whole set of epitopes from an original reference strain of SARS-CoV-2 originating in Wuhan, China, before proceeding to the next step.
The researchers discovered 1,222 epitopes of SARS-CoV-2 that were associated with major HLA subtypes, which covered approximately 90 percent of the human population; at least 9 out of every 10 people can mount a T cell response against COVID-19 based on these 1,222 epitopes, according to the researchers.
Next, the researchers performed a computational analysis to determine whether any of the 118,000 individual SARS-CoV-2 isolates from throughout the world, which was documented in a dataset from the National Center for Biotechnology Information (NCBI), had alterations in these epitopes.
According to their findings, 47 percent of the epitopes have been altered in at least one existing isolate. Existing isolates in some cases contained changes in numerous epitope locations, although cumulative mutations never affected more than 15 percent of epitopes for any given HLA allele type in any one year.
As a result of their investigation, the team discovered that susceptible alleles and the geographic origins of their respective escape isolates co-existed in some geographical regions, including sub-Saharan Africa, East, and Southeast Asia, indicating that there may be genetic pressure on the cytotoxic T cell response in these regions.
Despite this, the scientists conclude that the accumulation of these alterations in independent isolates is still too small to pose a hazard to the entire human population. “Using our approach, we were able to identify mutations that may be relevant for specific populations and that therefore merit further investigation.”
In the meantime, Martin-Galiano warns that “unnoticed SARS-CoV-2 alterations” could “threaten the cytotoxic T response in human subpopulations” in the future.