The properties of drug-vaccine delivery systems based on the use of biodegradable polymers, and its application in the control of experimental infection by Salmonella enterica serovar. Abortusovis (SAO), are described in this manuscript. Micelles of major membrane antigens from SAO (HSao extract) can be encapsulated in microparticles of poly(epsilon-caprolactone) or in nanoparticles of Gantrez polymer. The encapsulation process was optimized by the combined use of cyclodextrins. The resulting particles contained unaltered significant amounts of the antigenic complex. To establish the protective value of these subunit vaccines, particles were injected in one single dose (20 microg of HSao) subcutaneously in BALB/c mice in order to observe the protection conferred against experimental infection with the virulent strains S. Abortusovis 15/5. Control non-immunized animals resulted infected, as well as the group that received unloaded or HSao loaded into microparticles. In contrast, nanoparticles conferred a significant protection when compared to unvaccinated controls, similar to that induced by the attenuated commercial vaccine Rv6. In conclusion, protection against experimental infection in mice after one single shoot, and its potential for mucosal vaccination suggest that HSao-nanoparticles may represent a serious alternative to the conventional attenuated vaccines against S. Abortusovis.