is a host-adapted Gram-negative mammalian pathogen that causes the severe disease glanders. Glanders can manifest as a rapid acute progression or a chronic debilitating syndrome primarily affecting solipeds and humans in close association with infected animals. In USA, is classified as one of the most important bacterial biothreat agents. Presently, there is no licensed glanders vaccine available for humans or animals. In this work, outer membrane vesicles (OMVs) were isolated from three attenuated biosafe bacterial strains, Bp82, E555, and TxDOH and used to vaccinate mice. OMVs induced significantly higher antibody responses that were investigated. specific serum antibody responses were of higher magnitude in mice vaccinated with OMVs compared to levels in mice vaccinated with OMVs. OMVs derived from biosafe strains protected mice from acute lethal glanders with vesicles from the two strains affording significant protection (>90%) up to 35 days post-infection with some up to 60 days. Organ loads from 35-day survivors indicated bacteria colonization of the lungs, liver, and spleen while those from 60 days had high CFUs in the spleens. The highest antibody producing vaccine ( E555 OMVs) also protected C57BL/6 mice from acute inhalational glanders with evidence of full protection.