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-1beta 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.