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A Delta clpB Mutant of Francisella tularensis Subspecies holarctica Strain, FSC200, Is a More Effective Live Vaccine than F. tularensis LVS in a Mouse Respiratory Challenge Model of Tularemia
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi.
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi. (Arcum)
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2013 (Engelska)Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 8, nr 11, s. e78671-Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Francisella tularensis subsp. tularensis is a highly virulent pathogen for humans especially if inhaled. Consequently, it is considered to be a potential biothreat agent. An experimental vaccine, F. tularensis live vaccine strain, derived from the less virulent subsp. holarctica, was developed more than 50 years ago, but remains unlicensed. Previously, we developed a novel live vaccine strain, by deleting the chaperonin clpB gene from F. tularensis subsp. tularensis strain, SCHU S4. SCHU S4 Delta clpB was less virulent for mice than LVS and a more effective vaccine against respiratory challenge with wild type SCHU S4. In the current study, we were interested to determine whether a similar mutant on the less virulent subsp. holarctica background would also outperform LVS in terms of safety and efficacy. To this end, clpB was deleted from clinical holarctica strain, FSC200. FSC200 Delta clpB had a significantly higher intranasal LD50 than LVS for BALB/c mice, but replicated to higher numbers at foci of infection after dermal inoculation. Moreover, FSC200 Delta clpB killed SCID mice more rapidly than LVS. However, dermal vaccination of BALB/c mice with the former versus the latter induced greater protection against respiratory challenge with SCHU S4. This increased efficacy was associated with enhanced production of pulmonary IL-17 after SCHU S4 challenge.

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Public Library of Science , 2013. Vol. 8, nr 11, s. e78671-
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Mikrobiologi inom det medicinska området
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URN: urn:nbn:se:umu:diva-85560DOI: 10.1371/journal.pone.0078671ISI: 000327254700029PubMedID: 24236032Scopus ID: 2-s2.0-84893615965OAI: oai:DiVA.org:umu-85560DiVA, id: diva2:694622
Tillgänglig från: 2014-02-07 Skapad: 2014-02-06 Senast uppdaterad: 2023-03-23Bibliografiskt granskad

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Golovlev, IgorSjöstedt, Anders

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