• Nanoparticle-based COVID-19 vaccine coul

    From ScienceDaily@1:317/3 to All on Tue Mar 22 22:30:48 2022
    Nanoparticle-based COVID-19 vaccine could target future infectious
    diseases
    'Eventually there will be another emergent disease'

    Date:
    March 22, 2022
    Source:
    Northwestern University
    Summary:
    Just one dose of a new nanoparticle-based COVID-19 vaccine was
    enough to produce an immune response in animals on track with
    vaccines currently in clinical use. And with minor changes,
    researchers hope the same vaccine platform could target other
    infectious diseases.



    FULL STORY ==========================================================================
    Just one dose of a new nanoparticle-based COVID-19 vaccine was enough to produce an immune response in animals on track with vaccines currently in clinical use. And with minor changes, Northwestern University researchers
    hope the same vaccine platform could target other infectious diseases.


    ==========================================================================
    In a new study, 100% of mice who received the protein-based immunization survived when challenged with lethal doses of the SARS-CoV-2 virus,
    which causes COVID-19. None of the mice experienced lung damage due to SARS-CoV- 2 exposure. All mice who did not receive this nanoparticle
    vaccine died in a 14-day trial.

    The results, published this week in the Proceedings of the National
    Academy of Sciences, outline the structure-function relationships
    between the first spherical nucleic acid (SNA) vaccine developed to
    protect against viral infections.

    "What makes this vaccine different than other vaccines is the approach
    we take to design them," said Dr. Michelle Teplensky, co-first author
    of the paper.

    "Even as recently as a few years ago people focused on selecting the right target to train the immune system and the right stimulant to activate it,
    not on how those components were arranged structurally and presented to
    the body." Called SNAs, the nanoparticles that house the immune target
    are a form of globular DNA that can enter and stimulate immune cells
    with extreme efficiency.

    SNAs have been tested in more than 60 cell types. Researchers
    experimentally determined the ideal ratio between the SNA's shell and
    core density that produces the most potent response.

    SNA vaccines have been used to treat mice with triple negative breast
    cancer - - and more vaccines for other cancers are in development.



    ==========================================================================
    Chad A. Mirkin, the inventor of SNAs and the paper's corresponding author,
    led the study and said the platform can translate to infectious diseases.

    "This is a remarkable demonstration of rational vaccinology -- the
    idea that the structure of a vaccine, as opposed to just components,
    can have a profound influence on efficacy," Mirkin said. "While we have previously shown this to be the case for cancer immunotherapies, this
    is the first demonstration for an infectious disease." Mirkin is the
    George B. Rathmann Professor of Chemistry in Northwestern's Weinberg
    College of Arts and Sciences, director of the International Institute
    of Nanotechnology and member of the Robert H. Lurie Comprehensive Cancer
    Center of Northwestern University.

    Making the drug Vaccines typically take years to develop. But
    with COVID-19 came astonishing advancements in this arena. Mirkin
    challenged Teplensky, a postdoctoral fellow in Mirkin's lab, to work
    with Ph.D. student and co-first author Max Distler, to evaluate whether
    the SNA platform could be used to create a potent vaccine, and expand
    its scope of impact. The two finished the project in just nine months -
    - roughly the same amount of time as commercial developers.



    ========================================================================== Typical viral immunizations consist of a mixture of molecules from the
    virus (called antigens) that tell the immune system what its target will
    be (the virus), and other molecules (called adjuvants) stimulate the
    immune system to boost the body's ability to tackle that target when it
    appears later. Because the mixture isn't traditionally packaged together, researchers predict that cells within patients are not getting a potent
    dose of both antigens and adjuvants.

    That's where structure comes into play. Mirkin coined the term "rational vaccinology" to describe how co-delivery and timing of these two drugs
    via one nanoparticle can make vaccines more effective. Tiny changes
    at the nanoscale can have big implications for a vaccine's efficacy
    and predictability.

    Mirkin's team packaged the antigen (a portion from COVID-19's infamous
    spike protein) inside the core of an SNA, and used a specific sequence of
    DNA known to stimulate the immune system (adjuvant) as the radial shell surrounding the core. The researchers injected mice under the skin,
    causing an immune response to the spike protein, and then monitored
    antibody production in the weeks following injection.

    Challenging the results Two weeks following the injection, mice vaccinated
    with the SNA vaccine had the highest antibody production compared to
    those vaccinated with a simple saline mixture of the same components, even outperforming other formulations containing commercially used adjuvants
    (which have been used in formulations of shingles, Hepatitis B and flu vaccinations) by 14-fold.

    Antibodies correlate to protection against infection, establishing
    the platform's potential in the COVID-19 and infectious disease
    space. Protein- based vaccines also have fewer side effects and can
    be stored at normal refrigerator temperature, lowering production and distribution costs considerably.

    The researchers looked at papers from commercially available COVID-19 vaccinations and found other studies' final antibody production at two
    weeks was "right on track" with their own.

    Just to be sure, the team sent their vaccine off to Argonne National
    Laboratory and allowed them to be put to the test by vaccinating mice
    and then infecting them with high doses of the SARS-CoV-2 virus in
    a double-blind study. One hundred percent of mice dosed with the SNA
    vaccine survived through the end of the trial with no lung damage caused
    by COVID-19 pneumonia.

    Stopping future viruses Using COVID-19 as a case study to compare how
    well the vaccine worked was mainly practical. But it also calls attention
    to the broader implications of the SNA as an infectious disease platform.

    Teplensky says that COVID-19 caused a shift in behavior toward infectious diseases. "People didn't recognize and appreciate the emergent power that infectious disease can have," Teplensky said. "We saw an opportunity
    to use COVID as a case study to shed light on the shortcomings in the vaccination space." Distler said, "with this case study, although
    the results are quite impressive, the goal was not to compete with
    existing COVID vaccines. We're preparing for the next mutation, or the
    next disease in need of a highly structured vaccine because eventually
    there will be another emergent disease." According to the researchers,
    the platform could even be used to target something as complex as HIV.

    "The modularity of this approach implies that a quick tweak might
    only be required to make a new vaccine for a future virus, especially
    if what we've observed previously with the cancer vaccine works,"
    Mirkin said. "All we'd need to do is change what we're teaching the
    immune system to target." The paper, "Spherical Nucleic Acids as an
    Infectious Disease Vaccine Platform," came together as a collaboration
    between Northwestern scientists, physicians, and engineers, the Argonne National Laboratory and University of Chicago. The research was supported
    by the Air Force Office of Scientific Research (award FA9550-17-1-0348),
    the Polsky Urologic Cancer Institute of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University at Northwestern Memorial Hospital
    and the National Cancer Institute of the National Institutes of Health
    (under awards R01CA208783 and P50CA221747).


    ========================================================================== Story Source: Materials provided by Northwestern_University. Original
    written by Win Reynolds. Note: Content may be edited for style and length.


    ========================================================================== Journal Reference:
    1. Michelle H. Teplensky, Max E. Distler, Caroline D. Kusmierz, Michael
    Evangelopoulos, Haley Gula, Derek Elli, Anastasia Tomatsidou,
    Vlad Nicolaescu, Ian Gelarden, Anjana Yeldandi, Daniel Batlle,
    Dominique Missiakas, Chad A. Mirkin. Spherical nucleic acids as an
    infectious disease vaccine platform. Proceedings of the National
    Academy of Sciences, 2022; 119 (14) DOI: 10.1073/pnas.2119093119 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/03/220322150850.htm

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