Vaccination with a novel live attenuated strain of Francisella tularensis subsp. tularensis protects cynomolgus macaques against aerosol F. tularensis infection

Licensed vaccines against Francisella tularensis, a public health threat in some parts of the world and a potential bioterrorism agent, are lacking in Western countries. Existing tularemia vaccine candidates have not been promising in protecting against the most serious respiratory form of tularemia infection. Previous studies identified a novel live attenuated vaccine candidate, F. tularensis subsp. tularensis ΔclpB, that protected rodents against aerosol challenge with the most virulent biotype of Francisella. Characterization demonstrated that ΔclpB is amenable to modern manufacturing. Here, we evaluated further ΔclpB's protective capacities in Fischer 344 rats and in cynomolgus macaques. Results demonstrated that rats immunized intradermally with ΔclpB survived aerosol F. tularensis challenge with up to 100 median lethal doses administered one year after vaccination, accompanied by reduced clinical signs of infection as well as reduced histopathology and bacterial burdens in lungs and spleens. Moreover, intradermal ΔclpB vaccination protected macaques against at least 500 MLD of aerosol F. tularensis challenge administered one and three months after vaccination; vaccination ameliorated symptoms, bacterial burdens, and tissue pathology when tested one year after vaccination. Given the low incidence of tularemia in nature, these studies therefore lay the foundation for additional animal-based evaluations of efficacy and future safety evaluation of ΔclpB by clinical studies.