Prevention of Tularemia Using an Enhanced Live Attenuated Vaccine Strain

Summary Francisella tularensis (F. tularensis) is an intracellular and facultative bacterium that is the etiological agent of tularemia. Government concern over F. tularensis as a biowarfare agent has been raised due to its high virulence when aerosolized. In the laboratory setting, a live attenuated vaccine (LVS) based on the lipopolysaccahride of F. tularensis has been used to immunize high risk individuals, however this vaccine is not approved for general use and is characterized by potentially harmful side effects and incomplete immunity.

The investigators have discovered an attenuated mutant strain of F. tularensis that has expressed high efficacy and low toxicity in a murine model of tularemia. The novel viral strain involves a gene mutation that reduces biosynthesis of the wild O-type polysaccharide side chain. The mechanism of reduced virulence may originate from phase variations in the lipopolysaccharide (LPS) surface, which houses the O-type polysaccharide. Here, it is found that a different antigenic form of O-type polysaccharide is present in the LPS variant, which unlike the inert LPS form, is capable of stimulating a pro-inflammatory immune response characterized by nitric oxide production. In murine studies, reduction in O-type polysaccharide impaired viral dissemination to the reticuloendothelial organs and prevented virulence when tested in a murine tularemia model.

Applications The modified strain of F. tularensis is in evaluation as a vaccine. For Further Information Please Contact the Director of Business Development Katie Gordon Email: [email protected] Telephone: (617) 432-0920

Inventor(s): Kasper, Dennis

Type of Offer: Licensing



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