Rapid DNA vaccination against Burkholderia pseudomallei flagellin by tattoo or intranasal application.
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.
a Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam , Amsterdam , the Netherlands.
Jacqueline M
JM
Lankelma
a Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam , Amsterdam , the Netherlands.
Alex
A
Wagemakers
a Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam , Amsterdam , the Netherlands.
Emma
E
Birnie
a Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam , Amsterdam , the Netherlands.
Bastiaan W
BW
Haak
a Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam , Amsterdam , the Netherlands.
Jos J A
JJA
Trentelman
a Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam , Amsterdam , the Netherlands.
Tassili A F
TAF
Weehuizen
a Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam , Amsterdam , the Netherlands.
Jasmin
J
Ersöz
b Department of Pathology , Academic Medical Center, University of Amsterdam , Amsterdam , the Netherlands.
Joris J T H
JJTH
Roelofs
a Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam , Amsterdam , the Netherlands.|c Department of Internal Medicine , Division of Infectious Diseases, Academic Medical Center , Amsterdam , the Netherlands.
Joppe W
JW
Hovius
a Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam , Amsterdam , the Netherlands.|c Department of Internal Medicine , Division of Infectious Diseases, Academic Medical Center , Amsterdam , the Netherlands.
W Joost
WJ
Wiersinga
c Department of Internal Medicine , Division of Infectious Diseases, Academic Medical Center , Amsterdam , the Netherlands.
Adriaan D
AD
Bins
D000818:Animals; D001426:Bacterial Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D016957:Burkholderia pseudomallei / Q000235:genetics / Q000276:immunology*; D005260:Female; D005408:Flagellin / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D006801:Humans; D008554:Melioidosis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D013653:Tattooing / Q000379:methods*; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology
D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D019444:Vaccines, DNA; D005408:Flagellin
Burkholderia pseudomallei; DNA vaccines; flagellin; melioidosis; tattoo