Rapid DNA vaccination against Burkholderia pseudomallei flagellin by tattoo or intranasal application

Jacqueline M Lankelma1, Alex Wagemakers1, Emma Birnie1

  • 1a Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam , Amsterdam , the Netherlands.

Virulence
|March 22, 2017
PubMed

Insights

Rapid DNA vaccination using Burkholderia pseudomallei flagellin shows promise for melioidosis prevention. A single intranasal vaccine dose significantly reduced bacterial load and improved survival in mice, offering a potential rapid response strategy.

Area of Science:

  • Infectious Diseases
  • Vaccinology
  • Microbiology

Background:

  • Melioidosis, caused by Burkholderia pseudomallei, is a severe, high-mortality disease endemic in Southeast Asia and Northern Australia.
  • B. pseudomallei is a potential bioterrorism agent due to its virulence and ease of dissemination.
  • No licensed vaccine currently exists for melioidosis prevention.

Purpose of the Study:

  • To evaluate rapid plasmid DNA vaccination targeting B. pseudomallei flagellin for protection against respiratory melioidosis.
  • To compare different subcellular targeting designs for flagellin DNA vaccines.
  • To assess the efficacy of a single-dose intranasal vaccine formulation.

Main Methods:

  • C57BL/6 mice were vaccinated via skin tattoo on days 0, 3, and 6 before intranasal challenge with B. pseudomallei on day 21.
  • The most effective DNA vaccine construct was tested as a single dose administered via tattoo or intranasally.
  • Bacterial loads, cytokine responses, inflammation, and tissue damage were assessed 72 hours post-challenge.

Main Results:

  • A DNA vaccine encoding a cellular secretion signal provided the most effective protection via tattooing, reducing bacterial loads tenfold.
  • A single intranasal administration of this vaccine resulted in over 1000-fold lower bacterial loads and increased survival.
  • Pro-inflammatory cytokine responses and markers of distant organ damage were significantly reduced.

Conclusions:

  • Rapid flagellin DNA vaccination, particularly via intranasal administration, offers significant protection against B. pseudomallei challenge.
  • Single-dose intranasal vaccination is a highly effective strategy for melioidosis prevention, especially for acute mass vaccination scenarios.
  • Further research into intranasal flagellin DNA vaccines is warranted for potential public health applications.

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