Intranasal vaccination with a defined live attenuated vaccine strain (ΔFTN0109) induces protective immunity against heterotypic pulmonary bacterial challenge. (106.29)

Abstract

Abstract The need for an efficacious vaccine against the potential bioterrorism agent Francisella tularensis is a consequence of its low infectious dose, high mortality rate, and ability to be spread via aerosol, leading to pneumonic disease. FTN0109 is a novel protein that may be associated with the outer membrane of the bacterium and which is expressed across all subspecies of Francisella. In this study, we sought to determine the efficacy of ΔFTN0109 as a putative vaccine candidate. Using intramacrophage replication assays, ΔFTN0109 has been shown to be highly attenuated for growth. Moreover, the LD50 for this defined vaccine strain is >105 CFU in BALB/c and C57BL/6 mice following intranasal challenge in comparison to its parental strain U112 (LD50<10 CFU). Intranasal vaccination with ΔFTN0109 induces the expression of splenic antigen-specific IFN-γ and IL-2, with concurrent induction of preferential Th1 humoral responses (increased serum IgG2a over IgG1). Intranasal immunization with ΔFTN0109 confers complete protection in BALB/c mice against a subsequent pulmonary challenge with the heterotypic subspecies holarctica Live Vaccine Strain (LVS). Lungs, livers, and spleens of vaccinated and LVS-challenged mice exhibited significant reductions in bacterial burdens compared to mock-vaccinated and challenged animals. Current studies are ongoing to further clarify the mechanisms by which protection is conferred following vaccination with ΔFTN0109.