Vaccine Prophylaxis against Tularemia in Man

Foshay, Lee; Hesselbrock, W. H.; Wittenberg, H.; Rodenberg, A. H.

doi:10.2105/ajph.32.10.1131

Cited by 56 publications

(44 citation statements)

References 3 publications

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“…This finding stimulated Foshay to work to develop a killed tularemia vaccine that induced humoral immunity (54,55). A number of techniques were employed to prepare the killed bacterial cells, including heating, acetone, and phenol treatment, and the Foshay vaccines were administered to human volunteers with variable results.…”

Section: Development Of Nonliving Tularemia Vaccinesmentioning

confidence: 99%

Tularemia

et al. 2002

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Francisella tularensis is the etiological agent of tularemia, a serious and occasionally fatal disease of humans and animals. In humans, ulceroglandular tularemia is the most common form of the disease and is usually a consequence of a bite from an arthropod vector which has previously fed on an infected animal. The pneumonic form of the disease occurs rarely but is the likely form of the disease should this bacterium be used as a bioterrorism agent. The diagnosis of disease is not straightforward. F. tularensis is difficult to culture, and the handling of this bacterium poses a significant risk of infection to laboratory personnel. Enzyme-linked immunosorbent assay- and PCR-based methods have been used to detect bacteria in clinical samples, but these methods have not been adequately evaluated for the diagnosis of pneumonic tularemia. Little is known about the virulence mechanisms of F. tularensis, though there is a large body of evidence indicating that it is an intracellular pathogen, surviving mainly in macrophages. An unlicensed live attenuated vaccine is available, which does appear to offer protection against ulceroglandular and pneumonic tularemia. Although an improved vaccine against tularemia is highly desirable, attempts to devise such a vaccine have been limited by the inability to construct defined allelic replacement mutants and by the lack of information on the mechanisms of virulence of F. tularensis. In the absence of a licensed vaccine, aminoglycoside antibiotics play a key role in the prevention and treatment of tularemia

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Section: Development Of Nonliving Tularemia Vaccinesmentioning

confidence: 99%

Tularemia

et al. 2002

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“…Initial attempts to develop a tularemia vaccine focused on a killed vaccine, which was ineffective (2,3). Subsequently, an attenuated type B strain of F. tularensis obtained from the former Soviet Union was passaged in vitro and evaluated as a vaccine.…”

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confidence: 99%

Live Attenuated Mutants of Francisella tularensis Protect Rabbits against Aerosol Challenge with a Virulent Type A Strain

et al. 2014

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c Francisella tularensis, a Gram-negative bacterium, is the causative agent of tularemia. No licensed vaccine is currently available for protection against tularemia, although an attenuated strain, dubbed the live vaccine strain (LVS), is given to at-risk laboratory personnel as an investigational new drug (IND). In an effort to develop a vaccine that offers better protection, recombinant attenuated derivatives of a virulent type A strain, SCHU S4, were evaluated in New Zealand White (NZW) rabbits. Rabbits vaccinated via scarification with the three attenuated derivatives (SCHU S4 ⌬guaBA, ⌬aroD, and ⌬fipB strains) or with LVS developed a mild fever, but no weight loss was detected. Twenty-one days after vaccination, all vaccinated rabbits were seropositive for IgG to F. tularensis lipopolysaccharide (LPS). Thirty days after vaccination, all rabbits were challenged with aerosolized SCHU S4 at doses ranging from 50 to 500 50% lethal doses (LD 50 ). All rabbits developed fevers and weight loss after challenge, but the severity was greater for mock-vaccinated rabbits. The ⌬guaBA and ⌬aroD SCHU S4 derivatives provided partial protection against death (27 to 36%) and a prolonged time to death compared to results for the mock-vaccinated group. In contrast, LVS and the ⌬fipB strain both prolonged the time to death, but there were no survivors from the challenge. This is the first demonstration of vaccine efficacy against aerosol challenge with virulent type A F. tularensis in a species other than a rodent since the original work with LVS in the 1960s. The ⌬guaBA and ⌬aroD SCHU S4 derivatives warrant further evaluation and consideration as potential vaccines for tularemia and for identification of immunological correlates of protection.

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“…The first attempts to prepare a vaccine, carried out in the 1930s, were directed toward killing F. tularensis with nitric acid. This corpuscular vaccine was then completed by adding 0.5% of phenol (the so-called Foshay vaccine) [207,208]. The efficacy of this type of vaccine was subsequently tested on humans.…”

Section: Prophylaxismentioning

confidence: 99%

Putting the Jigsaw Together - A Brief Insight Into the Tularemia

Kubelková

Macela

2015

Open Life Sciences

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Tularemia is a debilitating febrile and potentially fatal zoonotic disease of humans and other vertebrates caused by the Gram-negative bacterium Francisella tularensis. The natural reservoirs are small rodents, hares, and possibly amoebas in water. The etiological agent, Francisella tularensis, is a non-spore forming, encapsulated, facultative intracellular bacterium, a member of the γ-Proteobacteria class of Gram-negative bacteria. Francisella tularensis is capable of invading and replicating within phagocytic as well as non-phagocytic cells and modulate inflammatory response. Infection by the pulmonary, dermal, or oral routes, respectively, results in pneumonic, ulceroglandular, or oropharyngeal tularemia. The highest mortality rates are associated with the pneumonic form of this disease. All members of Francisella tularensis species cause more or less severe disease Due to their abilities to be transmitted to humans via multiple routes and to be disseminated via biological aerosol that can cause the disease after inhalation of even an extremely low infectious dose, Francisella tularensis has been classified as a Category A bioterrorism agent. The current standard of care for tularemia is treatment with antibiotics, as this therapy is highly effective if used soon after infection, although it is not, however, absolutely effective in all cases.

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Vaccine Prophylaxis against Tularemia in Man

Cited by 56 publications

References 3 publications

Tularemia

Tularemia

Live Attenuated Mutants of Francisella tularensis Protect Rabbits against Aerosol Challenge with a Virulent Type A Strain

Putting the Jigsaw Together - A Brief Insight Into the Tularemia

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