Characterization of the Burkholderia mallei ∆tonB Mutant and its Potential as a Backbone Attenuated Strain for Vaccine Development
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In this study, a Burkholderia mallei ∆tonB mutant deficient in iron acquisition was constructed, characterized and evaluated for its protective properties in acute inhalational mouse models of glanders and melioidosis infection. Compared to wild type, the B. mallei ΔtonB exhibits slower growth kinetics, siderophore hypersecretion and the inability to utilize hemin, hemoglobin and myoglobin as iron sources. A series of animal challenge studies showed an inverse correlation between percent survival in BALB/c mice and iron-dependent B. mallei tonB mutant growth. Upon evaluation of the B. mallei ∆tonB mutant’s potential as a protective vaccine, 100% survival was achieved after wild-type challenge in those animals previously immunized with 1.5x104 CFU of the B. mallei ∆tonB mutant. At 21 days post immunization, B. mallei tonB vaccinated animals showed significantly higher levels of B. mallei specific IgG1, IgG2a and IgM compared to PBS vaccinated animals. At 48 h post-challenge, PBS-treated animals exhibited higher levels of serum inflammatory cytokines and more severe pathological effects in target organs compared to animals immunized with the B. mallei ∆tonB mutant. In a cross-protection study with Burkholderia pseudomallei, B. mallei ∆tonB mutant-immunized animals showed significant protection when evaluated in an acute inhalational melioidosis mouse model. While the wild-type was cleared in all the vaccination studies, animals failed to clear the B. mallei ∆tonB mutant, which was primarily recovered from the spleen. Although further work is need to reduce its long-term persistence, maintaining immunogenicity, the B. mallei ∆tonB mutant demonstrates great potential as backbone attenuated strain for vaccine development against both glanders and melioidosis.