Tularemia in BALB/c and C57BL/6 mice vaccinated with Francisella tularensis LVS and challenged intradermally, or by aerosol with virulent isolates of the pathogen: protection varies depending on pathogen virulence, route of exposure, and host genetic background

Chen, Wangxue; Shen, Hua; Webb, Ann; KuoLee, Rhonda; Conlan, J. Wayne

doi:10.1016/s0264-410x(03)00386-4

Cited by 103 publications

(123 citation statements)

References 25 publications

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“…route. As expected from our previous work [13,21], all shamimmunized mice died after challenge with the highly virulent type A strain by day 6 and the less virulent type B strain between days 7 and 8. In contrast, all LVS-immunized mice survived the challenge except one mouse that died on day 6 or 10, respectively, after i.d.…”

Section: Oral Lvs Immunization Protects Balb/c Mice Against Type a Ansupporting

confidence: 87%

“…2C). In contrast, as previously reported by us and others [13][14][15], i.d. LVS immunized Balb/c mice remained highly susceptible to respiratory challenge with ~50 cfu type A F. tularensis (Fig.…”

Section: Oral Lvs Immunization Protects Balb/c Mice Against Type a Ansupporting

confidence: 51%

“…Limited epidemiological evidence and experimental studies in human volunteers and animal models indicate that systemic vaccination with LVS provides solid protection against subsequent massive systemic challenge with highly virulent type A F. tularensis, and, to a lesser extent, against the airborne pathogen [4,5,8,11,[13][14][15][24][25][26]. This could be a concern because typhoidal tularemia, the deadliest form of the disease with a mortality rate of >30% if untreated, is thought to be initiated by inhalation of the pathogen and the respiratory route is considered a likely portal in the event of a bioterrorist attack [6].…”

Section: Discussionmentioning

confidence: 99%

“…Thus, like i.d. and aerosol LVS immunization against respiratory type A F. tularensis challenge in mice [13,15], the protective immunity induced by oral LVS immunization appears to be relatively short-lived.…”

Section: Oral Lvs Immunization Protects Balb/c Mice Against Type a Anmentioning

confidence: 99%

“…This vaccine, when given by scarification, protects well against subsequent exposure to large dose systemic and small dose aerosol challenge with type A F. tularensis, but appears to be less protective against large dose aerosol challenge [4,5,8,9]. These findings were mimicked in animal models of tularemia using monkeys, guinea pigs and mice [10][11][12][13][14]. Thus, continued efforts to explore improved tularemia vaccine formulations and/or alternative immunization strategies for effective control of respiratory infection with the highly virulent type A F. tularensis are warranted.…”

Section: Introductionmentioning

confidence: 99%

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Oral immunization of mice with the live vaccine strain (LVS) of Francisella tularensis protects mice against respiratory challenge with virulent type A F. tularensis

KuoLee

Harris

Conlan

et al. 2007

Vaccine

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Francisella tularensis is a gram-negative intracellular bacterium, and the causative agent of tularemia. The infection can be initiated by various routes and can manifest itself in several clinical forms with the disseminated typhoidal form initiated by inhalation being most fatal. The attenuated live vaccine strain (LVS), developed almost 50 years ago, remains the sole effective tularemia vaccine, which is still only available as an Investigational New Drug for at-risk individuals. This vaccine, when given by scarification, appears to provide solid protection against subsequent systemic infection with clinical strains of F. tularensis, but its efficacy against respiratory infection is less satisfactory. In this study, we evaluated the potential of oral immunization with LVS for eliciting protection against systemic and respiratory infection with virulent F. tularensis strains in a mouse model of tularemia. Oral LVS immunization was highly effective at protecting Balb/c mice against lethal systemic or respiratory challenges with type A and type B F. tularensis. Compared to shamimmunized mice, oral LVS-immunized mice showed significant reductions in burdens of virulent F. tularensis in the lung and spleen and milder tissue damage and inflammation in the liver. The immunization induced F. tularensis -specific antibody responses in the serum and bronchoalveolar lavage fluids, as well as antigen-specific splenocyte proliferation and IFN-γ and IL-2 production. The protective efficacy was related to the size of the immunizing dose but not the number of doses administered. Like other routes of LVS immunization in mice, the protective immunity induced by oral immunization was relatively short-lived. These results suggest that oral immunization should be explored further as an alternative vaccination strategy to combat tularemia.

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Section: Oral Lvs Immunization Protects Balb/c Mice Against Type a Ansupporting

confidence: 87%

Section: Oral Lvs Immunization Protects Balb/c Mice Against Type a Ansupporting

confidence: 51%