Live vaccine strain of Francisella tularensis: infection and immunity in mice

Abstract

The live vaccine strain (LVS) ofFrancisella tularensis caused lethal disease in several mouse strains. Lethality depended upon the dose and route of inoculation. The lethal dose for 50% of the mice (LD50) in four of six mouse strains (A/J, BALB/cHSD, C3H/HeNHSD, and SWR/J) given an intraperitoneal (i.p.) inoculation was less than 10 CFU. For the other two strains tested, C3H/HeJ and C57BL/6J, the i.p. log LD5* was 1.5 and 2.7, respectively. Similar susceptibility was observed in mice inoculated by intravenous (i.v.) and intranasal (i.n.) routes: in all cases the LD50 was less than 1,000 CFU. Regardless of the inoculation route (i.p., i.v., or i.n.), bacteria were isolated from spleen, liver, and lungs within 3 days of introduction of bacteria; numbers of bacteria increased in these infected organs over 5 days. In contrast to the other routes of inoculation, mice injected with LVS intradermally (i.d.) survived infection: the LD50 of LVS by this route was much greater than 105 CFU. This difference in susceptibility was not due solely to local effects at the dermal site of inoculation, since bacteria were isolated from the spleen, liver, and lungs within 3 days by this route as well. The i.d.-infected mice were immune to an otherwise lethal i.p. challenge with as many as 104 CFU, and immunity could be transferred with either serum, whole spleen cells, or nonadherent spleen cells (but not Ig+ cells). A variety of infectious agents induce different disease syndromes depending on the route of entry. Francisella LVS infection in mice provides a model system for analysis of locally induced protective effector mechanisms.

Role of TLR signaling inFrancisella tularensis-LPS-induced, antibody-mediated protection againstFrancisella tularensischallenge

“…Ft LVS (ATCC 29684) was grown in MH broth (Becton Dickinson Microbiology Systems, Franklin Lakes, NJ, USA), supplemented with 1% IsoVitaleX (Becton Dickinson Microbiology Systems), 0.1% glucose, and ferric pyrophosphoric acid (Sigma-Aldrich, St. Louis, MO, USA), and frozen aliquots were prepared as described [26]. MH agar was used as solid culture media [27][28][29][30]. Ft Schu S4 (Centers for Disease Control, Fort Collins, CO, USA) experiments were conducted in an approved Biosafety Level 3 laboratory by trained personnel at the University of Virginia (Charlottesville, VA, USA).…”

Protective B‐cell epitopes of Francisella tularensis O‐polysaccharide in a mouse model of respiratory tularaemia

“…8,9,11,12 B cells were also shown to be required for generation of memory to F. tularensis 13 and polyclonal IgG antibodies to F. tularensis were reported to transfer resistance against F. tularensis to naive hosts, including humans. [14][15][16][17][18][19][20][21][22][23] Identification of the protective B-cell antigens and epitopes will aid in the design of both vaccines and immunotherapeutics against F. tularensis. Furthermore, because of the linked recognition of antigens by B and T cells, identification of protective B-cell epitopes may also shed light on potentially protective T-cell epitopes.…”

Type IV pili‐mediated secretion modulates Francisella virulence

“…novicida (F. novicida) is infectious only for immunocompromised humans (Ellis et al, 2002). Inbred mice are highly susceptible and succumb to infection by all Francisella subspecies including F. novicida (Fortier et al, 1991;Kieffer et al, 2003). Similarly to the symptoms of human tularaemia, mouse infection results in a rapid development of severe systemic disease, likely due to the ability of Francisella to evade the host innate immune system (Dreisbach et al, 2000;Telepnev et al, 2003;Bosio and Dow, 2005).…”