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Immunopeptidomics-based design of mRNA vaccine formulations against Listeria monocytogenes

Author

Listed:
  • Rupert L. Mayer

    (VIB-UGent Center for Medical Biotechnology, VIB
    Ghent University
    VIB Proteomics Core, VIB
    Vienna BioCenter)

  • Rein Verbeke

    (Ghent University
    Cancer Research Institute Ghent (CRIG))

  • Caroline Asselman

    (VIB-UGent Center for Medical Biotechnology, VIB
    Ghent University
    Ghent University Hospital)

  • Ilke Aernout

    (Ghent University
    Cancer Research Institute Ghent (CRIG))

  • Adillah Gul

    (VIB-UGent Center for Medical Biotechnology, VIB
    Ghent University)

  • Denzel Eggermont

    (VIB-UGent Center for Medical Biotechnology, VIB
    Ghent University)

  • Katie Boucher

    (VIB-UGent Center for Medical Biotechnology, VIB
    Ghent University
    VIB Proteomics Core, VIB)

  • Fabien Thery

    (VIB-UGent Center for Medical Biotechnology, VIB
    Ghent University)

  • Teresa M. Maia

    (VIB-UGent Center for Medical Biotechnology, VIB
    Ghent University
    VIB Proteomics Core, VIB)

  • Hans Demol

    (VIB-UGent Center for Medical Biotechnology, VIB
    Ghent University
    VIB Proteomics Core, VIB)

  • Ralf Gabriels

    (VIB-UGent Center for Medical Biotechnology, VIB
    Ghent University)

  • Lennart Martens

    (VIB-UGent Center for Medical Biotechnology, VIB
    Ghent University)

  • Christophe Bécavin

    (Université Côte d’Azur, CNRS, IPMC)

  • Stefaan C. Smedt

    (Ghent University
    Cancer Research Institute Ghent (CRIG))

  • Bart Vandekerckhove

    (Cancer Research Institute Ghent (CRIG)
    Ghent University)

  • Ine Lentacker

    (Ghent University
    Cancer Research Institute Ghent (CRIG))

  • Francis Impens

    (VIB-UGent Center for Medical Biotechnology, VIB
    Ghent University
    VIB Proteomics Core, VIB)

Abstract

Listeria monocytogenes is a foodborne intracellular bacterial pathogen leading to human listeriosis. Despite a high mortality rate and increasing antibiotic resistance no clinically approved vaccine against Listeria is available. Attenuated Listeria strains offer protection and are tested as antitumor vaccine vectors, but would benefit from a better knowledge on immunodominant vector antigens. To identify novel antigens, we screen for Listeria peptides presented on the surface of infected human cell lines by mass spectrometry-based immunopeptidomics. In between more than 15,000 human self-peptides, we detect 68 Listeria immunopeptides from 42 different bacterial proteins, including several known antigens. Peptides presented on different cell lines are often derived from the same bacterial surface proteins, classifying these antigens as potential vaccine candidates. Encoding these highly presented antigens in lipid nanoparticle mRNA vaccine formulations results in specific CD8+ T-cell responses and induces protection in vaccination challenge experiments in mice. Our results can serve as a starting point for the development of a clinical mRNA vaccine against Listeria and aid to improve attenuated Listeria vaccines and vectors, demonstrating the power of immunopeptidomics for next-generation bacterial vaccine development.

Suggested Citation

  • Rupert L. Mayer & Rein Verbeke & Caroline Asselman & Ilke Aernout & Adillah Gul & Denzel Eggermont & Katie Boucher & Fabien Thery & Teresa M. Maia & Hans Demol & Ralf Gabriels & Lennart Martens & Chri, 2022. "Immunopeptidomics-based design of mRNA vaccine formulations against Listeria monocytogenes," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33721-y
    DOI: 10.1038/s41467-022-33721-y
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    References listed on IDEAS

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    1. Claire Maudet & Marouane Kheloufi & Sylvain Levallois & Julien Gaillard & Lei Huang & Charlotte Gaultier & Yu-Huan Tsai & Olivier Disson & Marc Lecuit, 2022. "Bacterial inhibition of Fas-mediated killing promotes neuroinvasion and persistence," Nature, Nature, vol. 603(7903), pages 900-906, March.
    2. Alejandro Toledo-Arana & Olivier Dussurget & Georgios Nikitas & Nina Sesto & Hélène Guet-Revillet & Damien Balestrino & Edmund Loh & Jonas Gripenland & Teresa Tiensuu & Karolis Vaitkevicius & Mathieu , 2009. "The Listeria transcriptional landscape from saprophytism to virulence," Nature, Nature, vol. 459(7249), pages 950-956, June.
    3. Stefan Köster & Katharina van Pee & Martina Hudel & Martin Leustik & Daniel Rhinow & Werner Kühlbrandt & Trinad Chakraborty & Özkan Yildiz, 2014. "Crystal structure of listeriolysin O reveals molecular details of oligomerization and pore formation," Nature Communications, Nature, vol. 5(1), pages 1-14, September.
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