A new study of modeling published in the scientific journalPLOS Computational Biology‘ for Antonio Martin-Galianoof Carlos III Health Institute (ISCIII) has identified a number of existing strains of SARS-CoV-2, as well as other future variants that could arise, that have the potential to escape to the response of cytotoxic T cells of the immune system in a part of the population.
The T cell response in humans is genetically encoded by HLA molecules, meaning that different individuals have different HLAs, programmed to recognize invading pathogens based on different parts, or “epitopes,” of the pathogens.
With thousands of different HLA molecules in the human population and thousands of possible epitopes in any given virus, experimental evaluation of the immune response of each human HLA allele to each viral variant is not feasible. However, computational methods can facilitate this task.
In this new study, the researchers first determined the complete set of epitopes of a original reference strain of SARS-CoV-2 from Wuhan (China). The team discovered 1,222 SARS-CoV-2 epitopes associated with major HLA subtypes, covering approximately 90% of the human population; at least 9 out of 10 people can mount a T-cell response to covid-19 based on these 1,222 epitopes.
In geographic regions
The researchers then computationally analyzed whether any of the 118,000 different SARS-CoV-2 isolates from around the world had mutations in these epitopes. 47% of the epitopes were mutated in at least one extant isolate. In some cases, existing isolates had mutations in multiple epitope regions, but the cumulative mutations never affected more than 15% of the epitopes for any type of HLA allele.
When the team analyzed the susceptible alleles and the geographic origin of their respective escape isolates, they found that they coexisted in some geographic regions (including sub-Saharan Africa and East and Southeast Asia), suggesting a possible genetic pressure on the response of cytotoxic T cells in these areas.
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“The accumulation of these changes in independent isolates is still too low to threaten the global human population. Our protocol has identified mutations that may be relevant to specific populations and that warrant closer scrutiny“say the authors.
However, Martín-Galiano points out that “inadvertent mutations of SARS-CoV-2” could in the future “threaten the cytotoxic T response in human subpopulations.