• Vaccine Name: KKF24
• Target Pathogen: Francisella tularensis
• Target Disease: Tularemia
• Vaccine Ontology ID: VO_0000307
• Type: Live Attenuated
• IglC gene engineering:
  • Type: Protein
  • Description:
  • Detailed Gene Information: Click Here.
• Preparation: KKF24 is a recombinant strain of Francisella novicida U112 with iglC mutation (F. novicida delta-iglC::ermC) (Lauriano et al., 2003). Strains were grown at 37°C in Trypticase soy broth supplemented with 0.1% cysteine (Pammit et al., 2006).
• Virulence: KKF24 is highly attenuated for virulence in mice and growth within amoebae (Pammit et al., 2006).
• Description: KKF24 has been identified as a live attenuated vaccine against subsequent intranasal (i.n.) challenge with the wild-type organism of Francisella tularensis (Pammit et al., 2006).

Mouse Response

• Host Strain: BALB/c
• Vaccination Protocol: Mice were first anesthetized with 3% isoflurane using a rodent anesthesia system and then inoculated i.n. with 10^6 CFU of KKF24 in 25 μl of PBS. Mock-vaccinated animals were treated with PBS alone (Pammit et al., 2006).
• Persistence: (Pammit et al., 2006)
• Side Effects: None were noted (Pammit et al., 2006).
• Challenge Protocol: Vaccinated mice exhibited no signs of morbidity and were challenged 30 days later i.n. with escalating inocula of the wild-type F. novicida U112 strain. Animals were monitored daily for morbidity and mortality (Pammit et al., 2006).
• Efficacy: Intranasal vaccination with the F. novicida iglC mutant is highly efficacious against i.n. challenge with the wild-type strain (Pammit et al., 2006). Specifically, vaccinated animals challenged with 100 LD50 of U112 had an 82% survival rate, with minimal losses of body weight . When the challenge inoculum was increased to 1000 LD50 of U112, the survival rate decreased to 50%. Increasing the challenge inoculum further to 10,000 LD50 of U112 resulted in 20% survival. There was no survival of any unvaccinated animals at the challenge doses tested, indicating that all three inocula of U112 were lethal doses, as expected (Pammit et al., 2006).
• Host Ifng (Interferon gamma) response
  • Description: It was found that all of the IFN-γ−/− vaccinated mice quickly succumbed within 4 to 5 days to the pulmonary challenge with the wild-type strain, whereas 100% of the IFN-γ+/+ mice were completely protected against both challenge doses. Both groups were able to survive vaccination with KKF24 (Pammit et al., 2006).
  • Detailed Gene Information: Click Here.
• Host Ighg1 response
  • Description: Intranasal immunization with 106 CFU KKF24 induced a robust primary antibody response that included the induction of F. novicida-specific total, IgG1, and IgG2a antibodies. No binding was observed with unrelated antigens, levels in immune sera were significantly greater than normal mouse sera, and levels increased post-challenge (Pammit et al., 2006).
  • Detailed Gene Information: Click Here.
• Host Ighv1-9 response
  • Description: Intranasal immunization with 106 CFU KKF24 induced a robust primary antibody response that included the induction of F. novicida-specific total, IgG1, and IgG2a antibodies. No binding was observed with unrelated antigens, levels in immune sera were significantly greater than normal mouse sera, and levels increased post-challenge (Pammit et al., 2006).
  • Detailed Gene Information: Click Here.
• Host Il12a response
  • Description: There was potent IL-12 secretion from the stimulated cells upon i.n. vaccination with KKF24 as compared to mice inoculated with PBS. Cervical lymph node and spleen cells were stimulated by UV-inactivated KKF24 10 days after vaccination and then tested for cytokines (Pammit et al., 2006).
  • Detailed Gene Information: Click Here.