Immunopeptidomics-based design of highly effective mRNA vaccine formulations against Listeria monocytogenes
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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. To identify antigens for this bacterial pathogen that can be encoded in mRNA vaccine formulations, we screened for Listeria epitopes presented on the surface of infected human cell lines by mass spectrometry-based immunopeptidomics. In between more than 15,000 human self-peptides, we detected 68 Listeria epitopes from 42 different bacterial proteins, including several known antigens. Peptide epitopes presented on different cell lines were 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 resulted in high levels of protection in vaccination challenge experiments in mice. Our results pave the way for the development of a clinical mRNA vaccine against Listeria and demonstrate the power of immunopeptidomics for next-generation bacterial vaccine development.
INSTRUMENT(S): Orbitrap Fusion Lumos, Q Exactive HF
ORGANISM(S): Homo Sapiens (human) Listeria Monocytogenes Egd
TISSUE(S): Epithelial Cell, Cell Culture
DISEASE(S): Colon Cancer,Cervix Carcinoma
SUBMITTER: Rupert Mayer
LAB HEAD: Francis Impens
PROVIDER: PXD031451 | Pride | 2022-09-26
REPOSITORIES: pride
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