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Reintroduction of two deleted virulence loci restores full virulence to the live vaccine strain of Francisella tularensis
Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
Totalförsvarets forskningsinstitut FOI.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). (Sjöstedt)
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2009 (English)In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 77, no 8, 3424-3431 p.Article in journal (Refereed) Published
Abstract [en]

A disadvantage of several old vaccines is that the genetic events resulting in the attenuation are often largely unknown and reversion to virulence cannot be excluded. In the 1950s, a live vaccine strain, LVS, was developed from a type B strain of Francisella tularensis, the causative agent of tularemia. LVS, which is highly attenuated for humans but still virulent for mice by some infection routes, has been extensively studied and found to protect staff from laboratory-acquired tularemia. The efforts to improve biopreparedness have identified a demand for a vaccine against tularemia. Recently the rapid progress in genomics of different Francisella strains has led to identification of several regions of differences (RDs). Two genes carried within RDs, pilA, encoding a putative type IV pilin, and FTT0918, encoding an outer membrane protein, have been linked to virulence. Interestingly, LVS has lost these two genes via direct repeat-mediated deletions. Here we show that reintroduction of the two deleted regions restores virulence of LVS in a mouse infection model to a level indistinguishable from that of virulent type B strains. The identification of the two attenuating deletion events could facilitate the licensing of LVS for use in humans.

Place, publisher, year, edition, pages
2009. Vol. 77, no 8, 3424-3431 p.
Keyword [en]
iv pilin gene; tularemia vaccine; burkholderia-pseudomallei; pseudomonas-aeruginosa; aerogenic immunization; twitching motility; causative agent; attenuation; expression; adherence
National Category
Immunology in the medical area
Identifiers
URN: urn:nbn:se:umu:diva-35112DOI: 10.1128/IAI.00196-09PubMedID: 19506014OAI: oai:DiVA.org:umu-35112DiVA: diva2:329593
Available from: 2010-07-12 Created: 2010-07-12 Last updated: 2017-12-12Bibliographically approved

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Zingmark, CarlGolovliov, IgorSjöstedt, AndersForsberg, Åke

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Salomonsson, EmelieZingmark, CarlGolovliov, IgorSjöstedt, AndersForsberg, Åke
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Umeå Centre for Microbial Research (UCMR)Molecular Infection Medicine Sweden (MIMS)Clinical BacteriologyDepartment of Molecular Biology (Faculty of Science and Technology)
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Infection and Immunity
Immunology in the medical area

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