• Mutations leading to omicron variant did

    From ScienceDaily@1:317/3 to All on Fri Mar 11 21:30:42 2022
    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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