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Clinical and Vaccine Immunology, September 2008, p. 1322-1329, Vol. 15, No. 9
1071-412X/08/$08.00+0     doi:10.1128/CVI.00125-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Neisseria meningitidis PorB, a Toll-Like Receptor 2 Ligand, Improves the Capacity of Francisella tularensis Lipopolysaccharide To Protect Mice against Experimental Tularemia{triangledown}

Damiana Chiavolini,{dagger} Susan Weir,{dagger} John R. Murphy, and Lee M. Wetzler*

Department of Medicine, Boston University School of Medicine, Boston, Massachusetts

Received 7 April 2008/ Returned for modification 19 May 2008/ Accepted 30 June 2008

Francisella tularensis causes severe pneumonia that can be fatal if it is left untreated. Due to its potential use as a biological weapon, research is being conducted to develop an effective vaccine and to select and study adjuvant molecules able to generate a better and long-lasting protective effect. PorB, a porin from Neisseria meningitidis, is a well-established Toll-like receptor 2 ligand and has been shown to be a promising vaccine adjuvant candidate due to its ability to enhance the T-cell costimulatory activity of antigen-presenting cells both in vitro and in vivo. BALB/c mice were immunized with lipopolysaccharide (LPS) isolated from the F. tularensis subsp. holarctica live vaccine strain (LVS), with or without PorB from N. meningitidis, and the antibody levels induced during the vaccination regimen and the level of protection against intranasal challenge with LVS were determined. Antigen administered alone induced a specific F. tularensis LPS immunoglobulin M (IgM) response that was not maintained over the weeks and that conferred protection to only 25% of the mice. In contrast, F. tularensis LPS given in combination with neisserial PorB induced consistent levels of specific IgM throughout the immunization and increased the proportion of surviving mice to 70%. Postchallenge cytokine analysis showed that interleukin-6 (IL-6), monocyte chemoattractant protein 1, and gamma interferon were markers of mortality and that IL-1β was a correlate of survival, independent of the presence of PorB as an adjuvant. These data indicate that neisserial PorB might be an optimal candidate adjuvant for improving the protective effect of F. tularensis LPS and other subunit vaccines against tularemia, but there is still a need to test its efficacy against virulent type A and type B F. tularensis strains.

* Corresponding author. Mailing address: 650 Albany Street, Evans Biomedical Research Center, Boston University Medical School, Boston MA 02118, Phone: (617) 414-4394. Fax: (617) 414-5280. E-mail: lwetzler{at}bu.edu

{triangledown} Published ahead of print on 9 July 2008.

{dagger} These authors made equal contributions to this study.

Clinical and Vaccine Immunology, September 2008, p. 1322-1329, Vol. 15, No. 9
1071-412X/08/$08.00+0     doi:10.1128/CVI.00125-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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