This work describes the development of a nanoemulsion composition suitable for the topical administration of vaccines based on outer membrane vesicles. The application onto bare skin of outer membrane antigens from Salmonella enterica (size between 20 and 100 nm), included in a nanoemulsion, induced a clear specific antibody response. In contrast to other semisolid formulations used (i.e. simple and polyethyleneglycol ointments), the occlusive effect provided by the nanoemulsion together with the penetration enhancer effect of Labrasol® and Plurol® oleique, increased antigen uptake by epidermal and transfollicular routes. Nevertheless, when the antigenic complex was loaded into poly(anhydride) nanoparticles and then incorporated in the nanoemulsion, the specific IgG response in serum was significantly lower. These results suggest that the higher size of nanoparticles (about 230 nm) and their non-deformable nature could hamper the arrival of the antigen to the immunological inducer sites when administered on the skin. Immunohistochemistry analysis confirmed that these bacterial vesicles were able to penetrate the skin reaching the dermis only when antigens were administered in the form of nanoemulsion. Further research will determine the full potential of this formulation for topical application of this specific type of vaccines.