Antimicrobial resistance is a global health threat, and alternative therapeutic interventions to replace failing antibiotics are urgently needed. Vaccines are effective tools to combat bacterial infection and mitigate multi-drug resistance, however, the selection of bacterial antigens as vaccine candidates remains challenging. Here we use immunopeptidomics to mine for CD4 T-cell vaccine targets in methicillin-resistant Staphylococcus aureus - a clinically significant, antibiotic-resistant bacterium that is susceptible to T cell meditated control. We identified a novel, highly conserved, immunodominant CD4 T cell epitope in S. aureus that is derived from the core DNA binding protein Hu (Hup). This epitope is shared across a range of clinically relevant bacteria and cross-species reactive Hup specific CD4 T cells are found in both mice and humans. Immunisation with the Hup epitope resulted in the development of broadly protective CD4 T cell immunity capable of limiting disease severity following infection with different bacterial species, including S. aureus and Streptococcus pneumoniae. A vaccine incorporating antigenic targets derived from conserved core genes that are shared across bacterial species, can confer broad spectrum protection against a range of clinically significant bacteria, including antibiotic-resistant strains.
[doi:10.25345/C5WP9TM2V]
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: dendritic cell ; Mutu ; Staphylococcus aureus ; MHC II ; antigen presentation ; immunopeptidomics ; DatasetType:Proteomics ; DatasetType:Other (Immunopeptidomics)
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Linda Wakim, University of Melbourne, Australia |
| Submitting User: | abraun |
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