Outer Membrane Vesicles from <i>Caulobacter crescentus</i>: A Platform for Recombinant Antigen Presentation

Bacterial outer membrane vesicles (OMVs) are an emerging and attractive technology for the generation of vaccines. Their properties as natural adjuvants, size, acellularity, and comparative cost of production favor their use as vaccines. Two major caveats for the use of OMVs as vaccines are their biological safety, since OMVs can induce a severe and even fatal inflammatory response and that they are naturally produced in low amounts. In this study, we show that a strategy to induce the production of OMVs applied to the nonpathogenic bacterium <i>Caulobacter crescentus</i> results in a strain with good OMV yields. In comparison with the OMVs derived from <i>Escherichia coli</i> K-12, the OMVs from <i>C. crescentus</i> induce a lower inflammatory response in an <i>in vivo</i> murine model of acute inflammation and in a human cell assay. Also, only minor signs of pain in mice were observed even at high doses. The <i>C. crescentus</i> OMVs can be efficiently loaded with a recombinant protein and induce antibody production against it with an adjuvant effect, indicating that these OMVs are viable vehicles for the presentation of recombinant antigens. These results support the use of the OMVs obtained from <i>C. crescentus</i> as a safe and effective platform for the development of low-cost vaccines.