Neisseria meningitidisPorB, a Toll-Like Receptor 2 Ligand, Improves the Capacity ofFrancisella tularensisLipopolysaccharide To Protect Mice against Experimental Tularemia
| Autor: | Lee M. Wetzler, John R. Murphy, Damiana Chiavolini, Susan Weir |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Lipopolysaccharides
Microbiology (medical) medicine.medical_treatment Clinical Biochemistry Immunology Porins medicine.disease_cause Microbiology Tularemia Mice Adjuvants Immunologic Antigen medicine Animals Humans Immunology and Allergy Francisella tularensis Mice Inbred BALB C Attenuated vaccine biology Neisseria meningitidis Vaccine Research biology.organism_classification medicine.disease Antibodies Bacterial Survival Analysis Vaccination Immunoglobulin M biology.protein Cytokines Female Adjuvant |
| Zdroj: | Clinical and Vaccine Immunology. 15:1322-1329 |
| ISSN: | 1556-679X 1556-6811 |
| DOI: | 10.1128/cvi.00125-08 |
| Popis: | Francisella tularensiscauses 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 fromNeisseria 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 theF. tularensissubsp.holarcticalive vaccine strain (LVS), with or without PorB fromN. 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 specificF. tularensisLPS immunoglobulin M (IgM) response that was not maintained over the weeks and that conferred protection to only 25% of the mice. In contrast,F. tularensisLPS 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 ofF. tularensisLPS and other subunit vaccines against tularemia, but there is still a need to test its efficacy against virulent type A and type BF. tularensisstrains. |
| Databáze: | OpenAIRE |
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