Efficacy of the live attenuated Francisella tularensis vaccine (LVS) in a murine model of disease

A live attenuated vaccine Francisella tularensis live vaccine strain (LVS), that confers protection against tularemia infection in a number of animal models including man was developed during the 1960s in the US. In this study, we have established the median lethal dose (MLD) after intraperitoneal (i.p.) or intravenous (i.v.) delivery of NDBR Lot 4 F. tularensis LVS to be 4 cfu and 2.24 × 104 cfu, respectively, in BALB/c mice and less than 1 cfu and 1.29 × 104 cfu, respectively, in C57BL/6 mice. When delivered subcutaneously, the MLD for F. tularensis LVS was greater then 1 × 108 cfu in both strains of mouse. Using mouse models of systemic tularemia infection it was demonstrated that F. tularensis LVS immunised BALB/c mice were fully protected after challenge with approximately 1000 MLD of a strain of F. tularensis subsp. tularensis or a strain of F. tularensis subsp. holarctica. Under similar challenge conditions, protection in C57BL/6 mice was only evident against a subsp. holarctica strain. In BALB/c mice, protection against a subsp. holarctica strain was achieved 4 days after F. tularensis LVS immunisation whereas protection against a subsp. tularensis strain was only evident 14 days after F. tularensis LVS immunisation.