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Significance Thanks to their potent built-in adjuvanticity, bacterial outer membrane vesicles (OMVs) represent an attractive vaccine platform. However, their full-blown exploitation relies on the availability of efficient engineering strategies. This work provides strong experimental evidence that OMVs can be successfully decorated with heterologous antigens by channeling them to the lipoprotein transport machinery. Not only did lipidated antigens accumulate in the vesicular compartment at high levels but they also interfered with the acylation process of lipid A, thus substantially reducing the lipopolysaccharide-mediated reactogenicity, a major hurdle for vaccine applications. The approach was validated with 5Staphylococcus aureus antigens, and mice immunized with engineered OMVs were completely protected againstS. aureus challenge, paving the way for development of vaccines against this important pathogen.

Bacterial outer membrane vesicles engineered with lipidated antigens as a platform for Staphylococcus aureus vaccine