A ΔclpB 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

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DOIResolve DOI: http://doi.org/10.1371/journal.pone.0078671
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EditorSearch for: Kaufmann, Gunnar F.
TypeArticle
Journal titlePLoS ONE
ISSN1932-6203
Volume8
Issue11
Article numbere78671
Pages18
SubjectFrancisella tularensis; Vaccines; Mouse models; Respiratory infections; Cytokines; Chaperone proteins; Chemokines; Vaccination and immunization
AbstractFrancisella 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 S4ΔclpB 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. FSC200ΔclpB 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, FSC200ΔclpB 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.
Publication date
PublisherPLOS
LanguageEnglish
AffiliationHuman Health Therapeutics; National Research Council Canada
Peer reviewedYes
NPARC number23000448
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Record identifier52f0ccc3-4ef6-42c7-8358-9d349a24a032
Record created2016-07-19
Record modified2016-07-19
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