BACKGROUNDVaccine development is a laborious craftwork in which at least two main components must be defined: a highly immunogenic antigen and a suitable delivery method. Hence, the interplay of these elements could elicit the required immune response to cope with the targeted pathogen with a long-lasting protective capacity.OBJECTIVESHere we evaluate the properties ofEscherichia colispherical proteoliposomes - known as outer membrane vesicles (OMVs) - as particles with natural adjuvant capacities and as antigen-carrier structures to assemble an innovative prophylactic vaccine for Chagas disease.METHODSTo achieve this, genetic manipulation was carried out onE. coliusing an engineered plasmid containing the Tc24Trypanosoma cruziantigen. The goal was to induce the release of OMVs displaying the parasite protein on their surface.FINDINGSAs a proof of principle, we observed that native OMVs - as well as those carrying theT. cruziantigen - were able to trigger a slight, but functional humoral response at low immunization doses. Of note, compared to the non-immunized group, native OMVs-vaccinated animals survived the lethal challenge and showed minor parasitemia values, suggesting a possible involvement of innate trained immunity mechanism.MAIN CONCLUSIONThese results open the range for further research on the design of new carrier strategies focused on innate immunity activation as an additional immunization target and venture to seek for alternative forms in which OMVs could be used for optimizing vaccine development.