Researchers identify COVID-19 variants with potential to escape cellular immune response

Date:
February 10, 2022
Source:
PLOS
Summary:
A number of existing strains of SARS-CoV-2, as well as other
future variants that could arise, have the potential to escape
the immune system's cytotoxic T cell response in some portion of
the population, according to a new modeling study.



FULL STORY ==========================================================================
A number of existing strains of SARS-CoV-2, as well as other
future variants that could arise, have the potential to escape the
immune system's cytotoxic T cell response in some portion of the
population. That's the conclusion of a new modeling study publishing
Feb. 10 in PLOS Computational Biologyby Antonio Marti'n-Galiano of the
Carlos III Health Institute, Spain, and colleagues.


==========================================================================
The T cell response in humans is genetically encoded by HLA molecules
-- this means 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, the experimental
evaluation of the immune response of every human HLA allele to every viral variant is not feasible. However, computational methods can facilitate
this task.

In the new study, researchers first determined the full set of epitopes
from an original reference strain of SARS-CoV-2 from Wuhan, China. The
team discovered 1,222 epitopes of SARS-CoV-2 that were associated with
major HLA subtypes, covering about 90% of the human population; at least
9 out of every 10 people can launch a T cell response to COVID-19 based
on these 1,222 epitopes.

Then, the researchers computationally analyzed whether any of 118,000
different SARS-CoV-2 isolates from around the world, described in
a National Center for Biotechnology Information (NCBI) dataset, had
mutations in these epitopes. 47% of the epitopes, they showed, were
mutated in at least one existing isolate. In some cases, existing isolates
had mutations in multiple epitope regions, but cumulative mutations never affected more than 15% of epitopes for any given HLA allele type. When
the team analyzed susceptible alleles and the geographic origin of
their respective escape isolates, the team found that they co-existed
in some geographical regions -- including sub-Saharan Africa and East
and Southeast Asia -- , suggesting potential genetic pressure on the
cytotoxic T cell response in these areas.

"The accumulation of these changes in independent isolates is
still too low to threaten the global human population," the authors
say. "Our protocol has identified mutations that may be relevant for
specific populations and warrant deeper surveillance." However, Marti'n-Galiano notes that "unnoticed SARS-CoV-2 mutations" might
in future "threaten the cytotoxic T response in human subpopulations." ========================================================================== Story Source: Materials provided by PLOS. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Anna Foix, Daniel Lo'pez, Francisco Di'ez-Fuertes, Michael
J. McConnell,
Antonio J. Marti'n-Galiano. Predicted impact of the viral mutational
landscape on the cytotoxic response against SARS-CoV-2. PLOS
Computational Biology, 2022; 18 (2): e1009726 DOI: 10.1371/
journal.pcbi.1009726 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220210153238.htm

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