期刊
NPJ VACCINES
卷 6, 期 1, 页码 -出版社
NATURE RESEARCH
DOI: 10.1038/s41541-021-00281-z
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资金
- Defense Threat Reduction Agency [HDTRA1-14-C-0035]
Burkholderia pseudomallei OMVs produced under macrophage-mimicking growth conditions (M9 OMVs) contain proteins associated with intracellular survival, provide significant protection against pulmonary infection in mice, possess adjuvanticity, and may serve as a promising vaccine against melioidosis.
Burkholderia pseudomallei is a Gram-negative, facultative intracellular bacillus that causes the disease melioidosis. B. pseudomallei expresses a number of proteins that contribute to its intracellular survival in the mammalian host. We previously demonstrated that immunization with OMVs derived from B. pseudomallei grown in nutrient-rich media protects mice against lethal disease. Here, we evaluated if OMVs derived from B. pseudomallei grown under macrophage-mimicking growth conditions could be enriched with intracellular-stage proteins in order to improve the vaccine. We show that OMVs produced in this manner (M9 OMVs) contain proteins associated with intracellular survival yet are non-toxic to living cells. Immunization of mice provides significant protection against pulmonary infection similar to that achieved with a live attenuated vaccine and is associated with increased IgG, CD4(+), and CD8(+) T cells. OMVs possess inherent adjuvanticity and drive DC activation and maturation. These results indicate that M9 OMVs constitute a new promising vaccine against melioidosis.
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