Mice vaccinated with the O-antigen of Francisella tularensis LVS lipopolysaccharide conjugated to bovine serum albumin develop varying degrees of protective immunity against systemic or aerosol challenge with virulent type A and type B strains of the pathogen

Conlan, J. Wayne; Shen, Hua; Webb, Ann; Perry, Malcolm B.

doi:10.1016/s0264-410x(02)00345-6

Cited by 131 publications

(151 citation statements)

References 22 publications

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“…Levels of F. tularensis-specific antibodies in sera, fecal extracts and BAL fluid were measured by an enzyme-linked immunosorbent assay (ELISA) modified from a previously described procedure [12]. Briefly, 96-well Immulon 2 plates (Thermo Labsystems, Franklin, MA) were coated with sonicated whole-cell extracts (10 μg/ml protein; 100 μl/well) or purified LPS (5 μg/ml; 100 μl/well) of F. tularensis LVS in 0.1M sodium carbonate buffer (pH 9.5) at 4°C overnight.…”

Section: Detection Of F Tularensis-specific Antibodies By Elisamentioning

confidence: 99%

“…These data indicated that oral LVS immunization induces both systemic and mucosal antigen-specific antibody responses with a preferable IgG2a isotype. In this regard, although it is well-recognized that antibodies play a minor role in protection against virulent type A F. tularensis infection [12,24], the presence of systemic and mucosal Francisella-specific antibody responses, nevertheless, demonstrated the capacity of the oral immunization strategy to induce a local immune response in the lung.…”

Section: Induction Of Antigen-specific Systemic and Mucosal Immune Rementioning

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: Detection Of F Tularensis-specific Antibodies By Elisamentioning

confidence: 99%

Section: Induction Of Antigen-specific Systemic and Mucosal Immune Rementioning

confidence: 99%

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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“…In contrast, another type A strain, FSC033, originally isolated from a squirrel, proved highly virulent for a variety of mouse strains with an LD 100 of <10 cfu when administered either as an aerosol or via the i.d. route [8][9][10][11]. Consequently, it was used in all of our recent studies on F. tularensis infection and immunity [8][9][10][11][17][18][19].…”

Section: Virulence Of F Tularensis Isolates For Micementioning

confidence: 99%

“…In the intervening years LVS itself, because it retains residual virulence for mice, was used exclusively to reveal the molecular basis of host defences against the pathogen in murine models [reviewed in 6 and 7]. However, results obtained with LVS have rarely been predictive of those recently obtained using virulent strains of the pathogen [8][9][10][11][12]. Currently, concerns about biosecurity have rekindled research interest in type A F. tularensis infection and immunity [13].…”

Section: Introductionmentioning

confidence: 99%

Virulence comparison in mice of distinct isolates of type A Francisella tularensis

Twine

Shen

Kelly

et al. 2006

Microbial Pathogenesis

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Francisella tularensis subspecies tularensis (type A F. tularensis) is considered to be one of the most virulent of all bacterial pathogens. Mice are extremely susceptible to infection with this subspecies (LD 100 via various inoculation routes is <10 cfu). However, it has not been established whether overt virulence differences exist amongst type A strains of F. tularensis. To this end, the present study compared the virulence of two distinct type A strains, FSC033 and SCHU S4, for naïve mice and mice immunized with the live vaccine strain of the pathogen, F. tularensis LVS. One nominal isolate of SCHU S4 was found to be completely avirulent. Another isolate was highly virulent, but all examined cases appeared somewhat less virulent than FSC033. The implication of these findings for future infection and immunity studies is discussed.

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Prevention and Treatment of Biological Weapons‐Related Infection and Disease

Setlak¹

2005

Encyclopedia of Bioterrorism Defense

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The use of biological weapons against man is a recognized threat, especially after the dispersal of anthrax in fall 2001 and the continued risk from terrorist organizations throughout the world. In light of this threat, it is crucial to differentiate and analyze the various therapeutic approaches for prevention and treatment of biological weapons‐related infection and disease. There are three main categories of pharmaceuticals that can be utilized to treat casualties brought on by biological weapon agents. These include the antibiotics, antivirals and vaccines and toxoids. Consistent research on an unprecedented scale is being emphasized in the area of biodefense at numerous locations, such as the U.S. National Institutes of Health (NIH). As a result, therapeutic information in the context of biological weapons is constantly evolving and expanding. Therefore, it is important to maintain a working knowledge of the field and keep abreast of changes, research and updates in such therapeutics relating to prevention and treatment of biological weapon agents.

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Mice vaccinated with the O-antigen of Francisella tularensis LVS lipopolysaccharide conjugated to bovine serum albumin develop varying degrees of protective immunity against systemic or aerosol challenge with virulent type A and type B strains of the pathogen

Cited by 131 publications

References 22 publications

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

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

Virulence comparison in mice of distinct isolates of type A Francisella tularensis

Prevention and Treatment of Biological Weapons‐Related Infection and Disease

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