Change search
ReferencesLink to record
Permanent link

Direct link
Differential ability of novel attenuated targeted deletion mutants of Francisella tularensis subspecies tularensis strain SCHU S4 to protect mice against aerosol challenge with virulent bacteria: effects of host background and route of immunization
NRC, Kanada.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. (Sjöstedt ; Arcum)
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. (Sjöstedt)
Show others and affiliations
2010 (English)In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 28, no 7, 1824-1831 p.Article in journal (Refereed) Published
Abstract [en]

Francisella tularensis subspecies tularensis is a highly virulent facultative intracellular pathogen of humans and a potential biological weapon. A live vaccine strain, F. tularensis LVS, was developed more than 50 years ago by pragmatic attenuation of a strain of the less virulent holarctica subspecies. LVS was demonstrated to be highly effective in human volunteers who were exposed to intradermal challenge with fully virulent subsp. tularensis, but was less effective against aerosol exposure. LVS faces regulatory hurdles that to date have prevented its licensure for general use. Therefore, a better defined and more effective vaccine is being sought. To this end we have created gene deletion mutants in the virulent subsp. tularensis strain and tested them for their ability to elicit a protective immune response against systemic or aerosol challenge with the highly virulent wild-type subsp. tularensis strain, SCHU S4. Both oral and intradermal (ID) primary vaccination routes were assessed in BALB/c and C3H/HeN mice as was oral boosting. One SCHU S4 mutant missing the heat shock gene, clpB, was significantly more attenuated than LVS whereas a double deletion mutant missing genes FTT0918 and capB was as attenuated as LVS. In general mice immunized with SCHU S4DeltaclpB were significantly better protected against aerosol challenge than mice immunized with LVS. A single ID immunization of BALB/c mice with SCHU S4DeltaclpB was at least as effective as any other regimen examined. Mice immunized with SCHU S4Delta0918DeltacapB were generally protected to a similar degree as mice immunized with LVS. A preliminary examination of immune responses to vaccination with LVS, SCHU S4DeltaclpB, or SCHU S4Delta0918DeltacapB provided no obvious correlate to their relative efficacies.

Place, publisher, year, edition, pages
2010. Vol. 28, no 7, 1824-1831 p.
Keyword [en]
Francisella tularensis; Mutants; Vaccines; Aerosol
National Category
Immunology in the medical area
URN: urn:nbn:se:umu:diva-42613DOI: 10.1016/j.vaccine.2009.12.001ISI: 000275158500024PubMedID: 20018266OAI: diva2:409828
Available from: 2011-04-11 Created: 2011-04-11 Last updated: 2016-05-24Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Golovliov, IgorZingmark, CarlSjöstedt, Anders
By organisation
Clinical Bacteriology
In the same journal
Immunology in the medical area

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 45 hits
ReferencesLink to record
Permanent link

Direct link