Abstract
Melioidosis is an emerging disease that is caused by the facultative intracellular pathogen Burkholderia pseudomallei. It is intrinsically resistant to many antibiotics and host risk factors play a major role in susceptibility to infection. Currently, there is no human or animal vaccine against melioidosis. In this study, multiple B. pseudomallei MSHR668 deletion mutants were evaluated as live attenuated vaccines in the sensitive BALB/c mouse model of melioidosis. The most efficacious vaccines after an intraperitoneal challenge with 50-fold over the 50% median lethal dose (MLD50) with B. pseudomallei K96243 were 668 ΔhisF and 668 ΔilvI. Both vaccines completely protected mice in the acute phase of infection and showed significant protection (50% survivors) during the chronic phase of infection. The spleens of the survivors that were examined were sterile. Splenocytes from mice vaccinated with 668 ΔhisF and 668 ΔilvI expressed higher amounts of IFN-γ after stimulation with B. pseudomallei antigens than splenocytes from mice vaccinated with less protective candidates. Finally, we demonstrate that 668 ΔhisF is nonlethal in immunocompromised NOD/SCID mice. Our results show that 668 ΔhisF and 668 ΔilvI provide protective cell-mediated immune responses in the acute phase of infection and promote long term survival in the sensitive BALB/c mouse model of melioidosis.
Highlights
Melioidosis is an emerging disease that is endemic in Southeast Asia and Northern Australia, and is caused by the Gram-negative, facultative intracellular pathogen Burkholderia pseudomallei.The organism can be found in soil and water and has been reported to be distributed in a much wider range of territory that includes areas of the Middle East, Africa, South America, and CentralAmerica [1]
We examined a variety of attenuated mutants of B. pseudomallei MSHR668 (Table 1) to identify potential melioidosis vaccine candidates
At the same time we examined B. thailandensis E555, a strain that naturally acquired a capsular polysaccharide gene cluster that is similar to the cluster present in B. pseudomallei [24]
Summary
Melioidosis is an emerging disease that is endemic in Southeast Asia and Northern Australia, and is caused by the Gram-negative, facultative intracellular pathogen Burkholderia pseudomallei.The organism can be found in soil and water and has been reported to be distributed in a much wider range of territory that includes areas of the Middle East, Africa, South America, and CentralAmerica [1]. Melioidosis is an emerging disease that is endemic in Southeast Asia and Northern Australia, and is caused by the Gram-negative, facultative intracellular pathogen Burkholderia pseudomallei. The organism can be found in soil and water and has been reported to be distributed in a much wider range of territory that includes areas of the Middle East, Africa, South America, and Central. Cases of melioidosis have occurred in these latter areas and it has been suggested that it has been under reported because of both lack of awareness of the presence of the pathogen and lack of clinical expectation of the disease. Pneumonia is the most common presentation of melioidosis, which suggest that inhalation may be a common route of infection with cases increasing during the rainy season. Secondary pneumonia may occur from inoculation of the pathogen at a distal site
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