• Antibodies improve in quality for months

    From ScienceDaily@1:317/3 to All on Tue Feb 15 21:30:40 2022
    Antibodies improve in quality for months after COVID-19 vaccination
    Rising antibody quality may partially compensate for falling levels

    Date:
    February 15, 2022
    Source:
    Washington University School of Medicine
    Summary:
    Antibodies elicited by COVID-19 vaccination become steadily more
    powerful for at least six months after vaccination, according to
    a new study.



    FULL STORY ==========================================================================
    For at least six months after COVID-19 vaccination, antibodies produced
    by immune cells become steadily more formidable and more precisely
    targeted against the virus that causes COVID-19, according to a study
    of the antibody response to the Pfizer-BioNTech vaccine by researchers
    at Washington University School of Medicine in St. Louis.


    ==========================================================================
    The idea that antibodies increase in quality as they decrease in quantity
    will come as no surprise to immunologists. The process was described
    in animals by Washington University immunologists Herman Eisen, MD,
    and Gregory Siskind, MD, in 1964. But this study, published Feb. 15 in
    Nature, is the first to track the maturation of the antibody response
    in detail in people.

    The findings suggest that declining antibody levels in the months after vaccination primarily represent a shift to a sustainable immune response.

    Producing vast quantities of antibodies burns a lot of energy. The
    immune system cannot sustain such a high level of activity indefinitely,
    so it gradually switches to producing smaller amounts of more powerful antibodies.

    Even quite low levels of antibodies would continue to provide some
    protection against disease, the researchers said -- as long as the virus doesn't change.

    "If the virus didn't change, most people who got two doses of this
    vaccine would be in very good shape," said senior author Ali Ellebedy,
    PhD, an associate professor of pathology & immunology, of medicine and of molecular microbiology. "The antibody response we saw is exactly what we'd expect from a robust immune response. We never thought that six months following that second injection, many people would still be actively
    improving the quality of their antibodies. To me, that is remarkable. The problem is that this virus keeps evolving and producing new variants. So,
    the antibodies are getting better at recognizing the original strain,
    but unfortunately the target keeps changing." Immune cells that produce antibodies are from the B cell family. Following the B cell response
    through all of its stages -- from initiation through peak antibody
    production to the emergence of memory cells that can quickly churn
    out new antibodies the next time the body encounters the same virus --
    requires repeatedly taking samples from parts of the body that can be
    hard to access. At different stages in the process, key members of the
    B cell family are located in the blood, the lymph nodes and the bone
    marrow. Getting B cells from the lymph nodes is technically challenging
    and involves using ultrasound to locate minuscule immune structures
    called germinal centers within the lymph nodes.

    Obtaining a sample of bone marrow involves inserting a needle into the
    pelvic bone.



    ==========================================================================
    The researchers collected blood from 42 participants and lymph node
    samples from 15 participants before each person received his or her
    first dose of the Pfizer-BioNTech COVID-19 vaccine and at weeks three,
    four, five, seven, 15 and 29 afterward. The researchers also obtained
    bone marrow samples from 11 participants 29 and 40 weeks after the first vaccine dose.

    Eight people provided all three kinds of samples, allowing the researchers
    to track the development of the antibody response over time within
    those individuals. None of the eight had been infected with the virus
    that causes COVID-19, so their antibody responses were entirely due to vaccination. The research team was led by Ellebedy and co-first authors
    Wooseob Kim, PhD, a postdoctoral researcher, and Julian Q. Zhou, PhD,
    a staff scientist.

    The researchers found that B cells targeted against SARS-CoV-2 persisted
    in the germinal centers of all participants for months. Even six months
    after vaccination, 10 out of 15 people still had B cells in their
    germinal centers.

    Germinal centers are like boot camps where B cells are trained to make
    ever- better-quality antibodies. The more time B cells spend in germinal centers, the more potent their antibodies get. Germinal centers had
    been thought to last only a few weeks, so finding these boot camps still training B cells in a majority of people so long after vaccination was a surprise, Ellebedy said, and an indication of a strong antibody response
    that continued to mature and improve.

    Indeed, six months after vaccination, the antibodies were noticeably
    better than they had been in the beginning. In one set of experiments,
    the researchers found that only 20% of early antibodies bound to a protein
    from the virus. Six months later, nearly 80% of antibodies from the same individuals bound to the viral protein.

    "When you look at antibodies, quantity should not be your only concern," Ellebedy said. "The antibodies at six months might be less in quantity,
    but they are much better in quality. And that refinement of the antibody response happens on its own. You get your shot, maybe your arm hurts for
    a day, and then you forget about it. But six months later your germinal
    centers are still ongoing and your antibodies are still getting better
    and better." The quality of the antibodies, of course, is measured
    against the original virus that was used to design the vaccine. If a new variant is different enough from the original, it may be able to escape once-powerful antibodies. Ellebedy and colleagues have begun studying
    the effects of variant-specific boosters on the antibody response to vaccination.

    "Everything changes when a new variant comes," Ellebedy said. "You have
    to retrain your immune system. It's like updating your anti-malware
    software to make sure it matches the newest computer viruses that are
    going around. It doesn't mean the old software was bad. It just means
    it no longer completely matches the viruses it is going to encounter." ========================================================================== Story Source: Materials provided by
    Washington_University_School_of_Medicine. Original written by Tamara
    Bhandari. Note: Content may be edited for style and length.


    ========================================================================== Journal Reference:
    1. Wooseob Kim, Julian Q. Zhou, Stephen C. Horvath, Aaron J. Schmitz,
    Alexandria J. Sturtz, Tingting Lei, Zhuoming Liu, Elizaveta
    Kalaidina, Mahima Thapa, Wafaa B. Alsoussi, Alem Haile, Michael
    K. Klebert, Teresa Suessen, Luis Parra-Rodriguez, Philip A. Mudd,
    Sean P. J. Whelan, William D. Middleton, Sharlene A. Teefey, Iskra
    Pusic, Jane A. O'Halloran, Rachel M. Presti, Jackson S. Turner, Ali
    H. Ellebedy. Germinal centre-driven maturation of B cell response
    to mRNA vaccination. Nature, 2022; DOI: 10.1038/s41586-022-04527-1 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/02/220215095500.htm

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