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The need for an efficacious vaccine against  Francisella tularensis  is a consequence of its low infectious dose and high mortality rate if left untreated. This study sought to characterize a live attenuated subspecies  novicida -based vaccine strain (U112Δ iglB ) in an established second rodent model of pulmonary tularemia, namely the Fischer 344 rat using two distinct routes of vaccination (intratracheal [i.t.] and oral). Attenuation was verified by comparing replication of U112Δ iglB  with wild type parental strain U112 in F344 primary alveolar macrophages. U112Δ iglB  exhibited an LD 50 >10 7  CFU compared to the wild type (LD 50  = 5×10 6  CFU i.t.). Immunization with 10 7  CFU U112Δ iglB  by i.t. and oral routes induced antigen-specific IFN-γ and potent humoral responses both systemically (IgG2a>IgG1 in serum) and at the site of mucosal vaccination (respiratory/intestinal compartment). Importantly, vaccination with U112Δ iglB  by either i.t. or oral routes provided equivalent levels of protection (50% survival) in F344 rats against a subsequent pulmonary challenge with ∼25 LD 50  (1.25×10 4  CFU) of the highly human virulent strain SCHU S4. Collectively, these results provide further evidence on the utility of a mucosal vaccination platform with a defined subsp.  novicida  U112Δ iglB  vaccine strain in conferring protective immunity against pulmonary tularemia.

Mucosal Immunization with Live Attenuated Francisella novicida U112ΔiglB Protects against Pulmonary F. tularensis SCHU S4 in the Fischer 344 Rat Model