Melioidosis is a severe
infectious disease with a high mortality that is endemic in South-East Asia and Northern Australia. The causative pathogen, Burkholderia pseudomallei, is listed as potential bioterror weapon due to its high virulence and potential for easy dissemination. Currently, there is no licensed
vaccine for prevention of
melioidosis. Here, we explore the use of rapid plasmid
DNA vaccination against B. pseudomallei
flagellin for protection against respiratory challenge. We tested three
flagellin DNA vaccines with different subcellular targeting designs. C57BL/6 mice were vaccinated via skin
tattoo on day 0, 3 and 6 before intranasal challenge with B. pseudomallei on day 21. Next, the most effective construct was used as single vaccination on day 0 by
tattoo or intranasal formulation. Mice were sacrificed 72 hours post-challenge to assess bacterial loads,
cytokine responses,
inflammation and microscopic lesions. A construct encoding a cellular secretion signal resulted in the most effective protection against
melioidosis via
tattooing, with a 10-fold reduction in bacterial loads in lungs and distant organs compared to the empty vector. Strikingly, a single
intranasal administration of the same
vaccine resulted in >1000-fold lower bacterial loads and increased survival. Pro-inflammatory
cytokine responses were significantly diminished and strong reductions in markers for distant organ damage were observed. A rapid vaccination scheme using
flagellin DNA tattoo provides significant protection against intranasal challenge with B. pseudomallei, markedly improved by a single administration via airway mucosa. Hence intranasal vaccination with
flagellin-encoding
DNA may be applicable when acute mass vaccination is indicated and warrants further testing.