Mice infected with a DUR1,2 deleted strain show greater survival and a more balanced immune response with less persistent neutrophil infiltration into the kidney. Thus, Dur1,2p appears to act locally in the kidney to create a pro-inflammatory state that is detrimental to the host. This could account for the greater renal malfunction and mortality in mice infected with WT C. albicans compared with the mutant lacking Dur1,2p. Correspondingly, a pharmacological inhibitor of Dur1,2p could improve patient survival of disseminated candidiasis by improving the innate immune response to kidney infections. Recently, we and others have begun to characterize the Fischer 344 rat as a potential second rodent model for pulmonary tularemia vaccine studies. We have demonstrated that F. Pimozide tularensis replicates within hepatocytes and bone marrow derived macrophages and that the rat may better reflect human susceptibility to pulmonary tularemia as evidenced by the LD50 of each subspecies when administered intratracheally. Rats challenged i.t. with human virulent subspecies holarctica and tularensis strains exhibited a mean time to death of 10 days and pulmonary LD50 values of approximately 105 and 500 CFU, respectively, as compared to the mouse where the LD50 of both subspecies is less than 10 CFU. Moreover, rats exhibit similar susceptibility as humans to the other subspecies of F. tularensis in comparison to mice. Thus, F344 rats may serve as a more reflective platform for evaluation of putative tularemia vaccine candidates. To this end, a successful vaccine against a respiratory pathogen such as F. tularensis will require induction of protective mucosal immunity at the site of infection. Various routes have been exploited to determine the most effective site to stimulate mucosal and systemic immunity including ocular, sublingual, intranasal/intratracheal, oral, intravaginal and intrarectal. For F. tularensis, the main routes of vaccination exploited have been subcutaneous, intranasal/intratracheal, intradermal, and oral. Protection against pulmonary F. tularensis challenge in animal models has demonstrated a role for both cellular and humoral arms of the immune system since B cells, IgA and CD4 + T cells, NK and CD8 + T cells as well as IFN-c and Th1 type responses have been shown by different investigators to assist in clearance of F. tularensis. To this end, protection also can be enhanced by the use of IL-12 as an adjuvant. Among these vaccination routes, the oral and 4-(Benzyloxy)phenol intranasal routes have received considerable attention for the ability to target microfold cells, located in Peyer’s patches within the gastrointestinal tract or nasal-associated lymphoid tissue in the respiratory tract, as induction sites. Mucosal immunization has been exploited as a successful route for vaccination against a variety of pathogens that infect the respiratory and gastrointestinal tracts. The licensed intranasal vaccine FluMist has been used successfully against seasonal influenza; and oral vaccination platforms also have been effectively used against other pathogens, most notably poliovirus, typhoid fever, and rotavirus. In this study, we sought to analyze and compare two routes of mucosal vaccination in the Fischer 344 rat utilizing a live attenuated vaccine strain that has been previously characterized in the mouse model of F. tularensis. This live attenuated strain lacks the iglB gene within the iglABCD operon of the Francisella pathogenicity island, consisting of 17 genes. Two copies of the FPI are found in the highly human virulent subsp. tularensis and holarctica, whereas a single copy of the FPI is found in subsp. novicida. There is.97% homology between the FPIs across subspecies, and genes of the FPI are required for intramacrophage replication, phagosomal escape, and virulence.