• Vaccine Name: F. tularensis vaccine X4072(pTUIA-15)
• Target Pathogen: Francisella tularensis
• Target Disease: Tularemia
• Vaccine Ontology ID: VO_0011548
• Type: Recombinant vector vaccine
• Status: Research
• Antigen: F. tularensis 17 kDa major membrane protein (TUL4) precursor
• TUL4 gene engineering:
  • Type: Recombinant vector construction
  • Description: A 1.0-kb EcoRV-SphI DNA fragment was prepared by the technique of Birnboim and Doly (6) from the plasmid pTUL4-9 (39), a derivative of pUC18. The fragment contains the gene encoding the T-cell-reactive 17-kDa protein TUL4 but contains no other expressed open reading frames (40). The isolated 1.0-kb fragment was ligated to the Asd+ plasmid pYA248 (27) after the plasmid had been cleaved with EcoRI and SphI and after the EcoRI site had been made blunt by using the Klenow fragment. The translation initiation codon of pYA248 was followed by a short sequence of 36 putatively encoding nucleotides of the Francisella DNA. The recombinant plasmid, denoted pTULA-15, was transformed (16, 20) into S. typhimunium x3730. By using a lysate of the X3730 recombinant, transduction of phage P22 HT int into X4072 was performed according to standard methods (12, 37). The presence of TUIA in lysates from transduced strains was confirmed by Western blot analysis, and one of the strains, denoted S. typhimurium X4072(pTUL4-15), was selected for the experiments (Sjöstedt et al., 1992).
  • Detailed Gene Information: Click Here.
• Immunization Route: Intraperitoneal injection (i.p.)

Mouse Response

• Host Strain: C57BL/10
• Vaccination Protocol: Mice were immunized twice, 4 weeks apart, by the intraperitoneal injection of 100 ,ll of PBS containing 5 x 10^3 (5 x 10^2 for the more susceptible mouse strain C57BL/10) organisms of S. typhimurium X4072 or S. typhimunum X4072(pTUIA-15) (Sjöstedt et al., 1992).
• Challenge Protocol: Three months after the completion of immunization, mice were intravenously challenged with F. tularensis LVS at a dose of 160 to 230 bacteria. At various intervals thereafter, mice were sacrificed for the enumeration of bacteria in the liver and spleen. The CFU per organ were recorded (Sjöstedt et al., 1992).
• Efficacy: A 17-kDa lipoprotein, TUL4, of the facultative intracellular bacterium Francisella tularensis is one of several membrane proteins that induce an in vitro response in T cells from F. tularensis-primed humans. When mice were immunized with S. typhimurium chi 4072(pTUL4-15), some animals showed an antibody response and a T-cell response to TUL4. The present study demonstrated that the 17-kDa lipoprotein TUL4 of F. tularensis is involved in a protective immunity to tularemia (Sjöstedt et al., 1992).