Immunopeptidomics-based design of mRNA vaccine formulations against Listeria monocytogenes

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, Christophe Bécavin, Stefaan C. Smedt, Bart Vandekerckhove, Ine Lentacker () and Francis Impens ()
Additional contact information
Rupert L. Mayer: VIB-UGent Center for Medical Biotechnology, VIB
Rein Verbeke: Ghent University
Caroline Asselman: VIB-UGent Center for Medical Biotechnology, VIB
Ilke Aernout: Ghent University
Adillah Gul: VIB-UGent Center for Medical Biotechnology, VIB
Denzel Eggermont: VIB-UGent Center for Medical Biotechnology, VIB
Katie Boucher: VIB-UGent Center for Medical Biotechnology, VIB
Fabien Thery: VIB-UGent Center for Medical Biotechnology, VIB
Teresa M. Maia: VIB-UGent Center for Medical Biotechnology, VIB
Hans Demol: VIB-UGent Center for Medical Biotechnology, VIB
Ralf Gabriels: VIB-UGent Center for Medical Biotechnology, VIB
Lennart Martens: VIB-UGent Center for Medical Biotechnology, VIB
Christophe Bécavin: Université Côte d’Azur, CNRS, IPMC
Stefaan C. Smedt: Ghent University
Bart Vandekerckhove: Cancer Research Institute Ghent (CRIG)
Ine Lentacker: Ghent University
Francis Impens: VIB-UGent Center for Medical Biotechnology, VIB

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-33721-y

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