Microbiology: Education, R&D and Market

Francisella tularensis subsp. tularensis (Ftt) is a highly virulent bacterium that causes the disease tularemia. Fewer than 10 bacteria are sufficient to cause a fatal infection when the bacteria are inhaled into the lung, therefore Ftt has been classified as a category A biothreat agent. F. novicida (Fn) is a closely-related species that is avirulent in healthy humans but causes a fatal disease in mice. We are developing Fn as a live vaccine strain to protect against Ftt infection. We have already shown that Fn with a mutation in iglD, the T6SS gene required for phagosome escape and intramacrophage replication (Fn-iglD), protects vaccinated animals against pulmonary challenge with Ftt using two different animal models, the Fischer 344 rat, and the cynomolgus macaque. To enhance the efficacy of Fn-iglD, we have engineered it to express the LPS O-antigen from Ftt (OAgFTT). The Fn-iglD strain expressing OAgFTT, KKF768, induces antibodies against OAgFTT in vaccinated mice and rats. Moreover, KKF768 vaccinated Fischer 344 rats are protected against lethal pulmonary challenge with Ftt, demonstrating that Fn iglD/OAgFTT is a good candidate for a tularemia vaccine.