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Reintroduction of two deleted virulence loci restores full virulence to the live vaccine strain of Francisella tularensis
Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
Totalförsvarets forskningsinstitut FOI.
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). (Sjöstedt)
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2009 (Engelska)Ingår i: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 77, nr 8, s. 3424-3431Artikel i tidskrift (Refereegranskat) 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.

Ort, förlag, år, upplaga, sidor
2009. Vol. 77, nr 8, s. 3424-3431
Nyckelord [en]
iv pilin gene; tularemia vaccine; burkholderia-pseudomallei; pseudomonas-aeruginosa; aerogenic immunization; twitching motility; causative agent; attenuation; expression; adherence
Nationell ämneskategori
Immunologi inom det medicinska området
Identifikatorer
URN: urn:nbn:se:umu:diva-35112DOI: 10.1128/IAI.00196-09PubMedID: 19506014Scopus ID: 2-s2.0-67651202552OAI: oai:DiVA.org:umu-35112DiVA, id: diva2:329593
Tillgänglig från: 2010-07-12 Skapad: 2010-07-12 Senast uppdaterad: 2023-03-24Bibliografiskt granskad

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Zingmark, CarlGolovliov, IgorSjöstedt, AndersForsberg, Åke

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Zingmark, CarlGolovliov, IgorSjöstedt, AndersForsberg, Åke
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Umeå Centre for Microbial Research (UCMR)Molekylär Infektionsmedicin, Sverige (MIMS)Klinisk bakteriologiInstitutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet)
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Infection and Immunity
Immunologi inom det medicinska området

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