Abstract
Burkholderia mallei 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, B. mallei 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, Burkholderia pseudomallei Bp82, B. thailandensis E555, and B. thailandensis TxDOH and used to vaccinate mice. B. thailandensis OMVs induced significantly higher antibody responses that were investigated. B. mallei specific serum antibody responses were of higher magnitude in mice vaccinated with B. thailandensis OMVs compared to levels in mice vaccinated with B. pseudomallei OMVs. OMVs derived from biosafe strains protected mice from acute lethal glanders with vesicles from the two B. thailandensis 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 (B. thailandensis E555 OMVs) also protected C57BL/6 mice from acute inhalational glanders with evidence of full protection.
Highlights
The disease glanders is primarily a zoonotic disease of solipeds that in ancient times was recognized by both Hippocrates and Aristotle [1]
Human cases of glanders were most often associated with individuals that were in close contact with infected horses, mules, or donkeys and was contracted through spreading of infectious secretions [3,4]
B. mallei strains (China 7, G-2(3), India 86-567-2, Ivan, SAVP1, and Turkey #1;), B. pseudomallei 1026b (CDC/United States Department of Agriculture (USDA) registered in house bacterial inventory) and B. thailandensis strains (E555, obtained from Mahidol University; and TxDOH, obtained from Centers for Disease Control and Prevention (CDC)) were grown on LB Lennox broth or agar (5 g/L NaCl) (LB, Fisher BioReagents, Pittsburgh, PA, USA) and grown at 37 ◦ C
Summary
The disease glanders is primarily a zoonotic disease of solipeds that in ancient times was recognized by both Hippocrates and Aristotle [1]. It is caused by the organism Burkholderia mallei, which is a host-adapted Gram-negative pathogen [2]. 20th century and its two World Wars, B. mallei has been associated with biological warfare, intentional misuse, and laboratory acquired infections [5,6,7]. It was used as a biological weapon in World War I by Germany and the Japanese in World War II researched human infections and intentional contamination of public water sources. The disease has been eradicated in North America, Australia, and most of Europe through careful surveillance, culling of infected animals and importation practices [8,9]
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