Recombinant Pseudomonas aeruginosa flagellin delivered using ferritin nanoparticles provides enhanced cross-protection against lung infection in mice

Increasing prevalence of multidrug- and pan-drug-resistant Pseudomonas aeruginosa (PA) strains has created an urgent need for an effective vaccine. Flagellin is an essential vaccine target because of its contribution to bacterial motility and other pathogenic processes. However, flagellin-based vaccines have not been successful thus far, probably due to a lack of efficient adjuvants or delivery systems. In this study, we genetically fused an A-type flagellin (FliC) to the self-assembled nanocarrier ferritin to construct the nanoparticle vaccine, reFliC-ferritin (reFliC-FN). reFliC-FN formed homogenous nanoparticles and induced a quick T helper 1 (Th1)-predominant immune response, which was quite different from that induced by recombinant FliC alone. In addition, reFliC-FN provided enhanced protection against PA strains carrying the A-type and heterogeneous B-type flagellins. Preliminary safety assays revealed the good biocompatibility and biosafety of reFliC-FN. Therefore, our data highlight the potential of ferritin as an ideal delivery system and suggest reFliC-FN as a promising PA vaccine candidate.