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Francisella tularensis  is one of the several biothreat agents for which a licensed vaccine is needed. To ensure vaccine protection is achieved across a range of virulent  F. tularensis  strains, we assembled and characterized a panel of  F. tularensis  isolates to be utilized as challenge strains. A promising tularemia vaccine candidate is rLVS Δ capB / iglABC  (rLVS), in which the vector is the LVS strain with a deletion in the  capB  gene and which additionally expresses a fusion protein comprising immunodominant epitopes of proteins IglA, IglB, and IglC. Fischer rats were immunized subcutaneously 1–3 times at 3-week intervals with rLVS at various doses. The rats were exposed to a high dose of aerosolized Type A strain Schu S4 (FRAN244), a Type B strain (FRAN255), or a tick derived Type A strain (FRAN254) and monitored for survival. All rLVS vaccination regimens including a single dose of 10 7  CFU rLVS provided 100% protection against both Type A strains. Against the Type B strain, two doses of 10 7  CFU rLVS provided 100% protection, and a single dose of 10 7  CFU provided 87.5% protection. In contrast, all unvaccinated rats succumbed to aerosol challenge with all of the  F. tularensis  strains. A robust Th1-biased antibody response was induced in all vaccinated rats against all  F. tularensis  strains. These results demonstrate that rLVS Δ capB / iglABC  provides potent protection against inhalational challenge with either Type A or Type B  F. tularensis  strains and should be considered for further analysis as a future tularemia vaccine.

human vaccines and immunotherapeutics

The rLVS Δ capB / iglABC  vaccine provides potent protection in Fischer rats against inhalational tularemia caused by various virulent  Francisella tularensis  strains