Mutations leading to omicron variant did not enable virus to fully
escape immune system
Study shows people with immunity to original SARS-CoV-2 likely maintain
some protection against omicron
Date:
March 11, 2022
Source:
Johns Hopkins Medicine
Summary:
People who gained immunity -- either through vaccination or
exposure - - against the original strain of SARS-CoV-2, the virus
that causes COVID- 19, also are likely to have some protection
against the pathogen's omicron variant, according to a new study.
FULL STORY ========================================================================== People who gained immunity -- either through vaccination or exposure
-- against the original strain of SARS-CoV-2, the virus that causes
COVID-19, also are likely to have some protection against the pathogen's omicron variant. That's because the mutations that led to the variant's emergence aren't found in the regions of the virus that stimulates
one type of cellular immune response, says an international research
team from Johns Hopkins Medicine, in collaboration with the National
Institute of Allergy and Infectious Diseases (NIAID) and ImmunoScape,
a U.S.-Singapore biotechnology company.
========================================================================== However, the researchers caution that their finding only relates to one
type of cell-mediated immunity -- the body's defense against invaders
that doesn't involve circulating antibodies -- and that it may be the antibody-related immune response (known as humoral immunity) that fails
when omicron causes so- called breakthrough infections.
The team's study was published March 1, 2022, in mBio, a journal from
the American Society for Microbiology.
"We found in a January 2021 study that in people previously infected
with the original COVID strain, specific epitopes [portions of a protein
that elicit an immune response] from the virus are recognized by immune
system cells known as CD8+ T lymphocytes, or killer T cells, and that this recognition enables a cell-mediated attack on COVID," says study lead
author Andrew Redd, Ph.D., assistant professor of medicine at the Johns
Hopkins University School of Medicine and staff scientist at NIAID. "In
our latest work, we found that these epitopes remained virtually untouched
by the mutations found in the omicron variant. Therefore, the CD8+ T cell response to omicron should be virtually as strong as it was to the initial
form of SARS-CoV-2." Other research groups in the United States and
South Africa have demonstrated very similar results for people previously infected by or vaccinated against the original SARS-CoV-2 strain.
CD8+ T cells are nicknamed killer T cells (they're also known as cytotoxic
T cells) for their ability to eliminate foreign invaders such as bacteria
and viruses from the body. The T cells used in the latest study were from
blood samples collected in 2020 from 30 patients who had recovered from
mild to moderate cases of COVID-19. The convalescent plasma donors had
six human leukocyte antigens (cell-surface proteins that regulate the
immune system and are part of each person's genetic profile), Redd says,
that are representative of greater than 73% of the U.S. population.
========================================================================== "This suggests that a significant portion of Americans who have been
vaccinated against or exposed to the original strain of SARS-CoV-2 might
have cytotoxic T cells that can produce an immune response to omicron,"
says study senior author Aaron Tobian, M.D., Ph.D., director of the
transfusion medicine division and professor of pathology at the Johns
Hopkins University School of Medicine.
The blood samples used in this study -- initially acquired for the
research team's earlier study of immune response in patients who were convalescent - - were taken from 26 to 62 days after the donors stopped
having COVID-19 symptoms. This enabled the donors' immune response to the
virus to be fully mature and yield CD8+ T cells primed against it. The
samples were stored after the researchers measured the T cell response.
During that assessment, donor samples were sent to ImmunoScape for
the difficult task of identifying which T cells had responded to
SARS-CoV-2. More specifically, the company's deep immune cell profiling
method showed which virus proteins elicited a T cell-directed response --
data that could provide valuable insight into the T cells' functional properties.
In the original analysis, the blood samples were probed with 408
different SARS-CoV-2 epitopes from spikes on the virus surface, from
the virus capsule and from nonstructural proteins inside the virus. The researchers found that T cells from the convalescent donors recognized
52 of the 408 epitopes.
Redd says that in the latest study, the researchers examined the 52
epitopes previously identified in the convalescent blood samples to
determine if they had been altered by escape mutations -- genetic changes
that would enable the virus to avoid being susceptible to cell-mediated immunity.
==========================================================================
"We only found one low-prevalence epitope from the omicron spike protein
that had a minor change from its predecessor in the original virus,"
says Redd.
"Overall, the omicron variant is known to have some 50-plus mutational differences between it and the original SARS-CoV-2 strain, but it seems
the virus has not evolved the ability to avoid T cell recognition."
While significant cell-mediated immunity appears to have been maintained
from the original SARS-CoV-2 through its subsequent variants, Redd,
Tobian and their colleagues say more research is needed to fully define
why people who have this protection may still get sick from omicron.
Along with Redd and Tobian, the members of the study team from Johns
Hopkins Medicine are Evan Bloch, Oliver Laeyendecker and Thomas
Quinn. Co-authors are Brian Abel, Michael Fehlings, Hassen Kared and
Alessandra Nardin from ImmunoScape, and Andrew Pekosz from the Johns
Hopkins Bloomberg School of Public Health.
The study was supported by NIAID grants R01AI120938, R01AI120938S1 and R01AI128779; the NIAID Division of Intramural Research; and National
Heart Lung and Blood Institute grant 1K23HL151826-01.
Abel, Fehlings, Kared and Nardin were ImmunoScape shareholders and/or
employees when the January 2021 study was conducted, and Nardin is a
board director for the company.
All other study authors report no conflicts of interest.
========================================================================== Story Source: Materials provided by Johns_Hopkins_Medicine. Note:
Content may be edited for style and length.
========================================================================== Journal Reference:
1. Andrew D. Redd, Alessandra Nardin, Hassen Kared, Evan M. Bloch,
Brian
Abel, Andrew Pekosz, Oliver Laeyendecker, Michael Fehlings,
Thomas C.
Quinn, Aaron A. R. Tobian. Minimal Crossover between Mutations
Associated with Omicron Variant of SARS-CoV-2 and CD8 T-Cell
Epitopes Identified in COVID-19 Convalescent Individuals. mBio,
2022; DOI: 10.1128/mbio.03617-21 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/03/220311095347.htm
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