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Vaccine Detail

Microencapsulated B. melitensis vjbR mutant vaccine
Vaccine Information
  • Vaccine Name: Microencapsulated B. melitensis vjbR mutant vaccine
  • Target Pathogen: Brucella spp.
  • Target Disease: Brucellosis
  • Vaccine Ontology ID: VO_0000398
  • Type: Live, attenuated vaccine
  • Antigen: An attenuated mutant of Brucella meletensis called vjbR::Tn5 (BMEII1116) is the antigen used in this vaccine (Arenas-Gamboa et al., 2008).
  • VjbR gene engineering:
    • Type: Gene mutation
    • Description: Live B. melitensis attenuated mutant vjbR::Tn5 was generated by mutation of the vjbR gene through interruption with a Tn5 (Arenas-Gamboa et al., 2008).
    • Detailed Gene Information: Click Here.
  • Preparation: 6 x 10^6 CFU of the live B. melitensis mutant bjvR::Tn5 was suspended in 1ml of MOPS buffer (buffer containing MOPS and NaCl) and mixed with 5 ml of alginate solution. Spheres were obtained by extruding the suspension through a 200 micron nozzle into a 100 mM calcium chloride solution and stirred for 15 minutes. After extrusion of the bacteria-alginate mixture into the CaCl2, the capsules were washed twice with MOPS for 5 minutes and further crosslinked with 0.05% poly-L-lysine for 10 minutes. Following two successive washes, the beads were stirred for five minutes in a solution of 0.03% (w/v) alginate to apply a final outer shell and washed twice with MOPS (Arenas-Gamboa et al., 2008).
  • Virulence: B. melitensis mutant bjvR::Tn5 is an attenuated live strain.
  • Storage: The vaccine was stored at 4°C (Arenas-Gamboa et al., 2008).
Host Response

Mouse Response

  • Host Strain: BALB/c
  • Vaccination Protocol: Sixty female BALB/c mice were randomly distributed into groups of 10 for intraperitoneally (IP) vaccination. Each animal was given a single dose of microcapsules containing 1 x 10^5 CFU of either: encapsulated B. melitensis mutant vjbR::Tn5 in alginate (vjbR::Tn5/alginate), encapsulated vjbR::Tn5 in alginate with VpB inside the capsule (vjbR::Tn5/VpB core), or encapsulated vjbR::Tn5 in alginate with VpB in the shell of the sphere (vjbR::Tn5/VpB shell). The control groups received 1 x 10^5 CFU of either nonencapsulated vjbR::Tn5, empty capsules (no bacteria entrapped), or two hundred microliters of MOPS buffer (Arenas-Gamboa et al., 2008).
  • Persistence: There appears to be a brief period between week one and two during which the organism replicates and the numbers of B. melitensis vjbR::Tn5 in the spleen increase, but by three weeks post-inoculation the number of organisms in the spleen exhibits a drastic decline and drops below the level of detection by four weeks post-infection (Arenas-Gamboa et al., 2008).
  • Immune Response: Immunization with BM vjbR::Tn5 elicited an IgG response that was clearly detectable after 2 weeks post-vaccination for either encapsulated or nonencapsulated vaccines. In mice vaccinated with the nonencapsulated BM vjbR::Tn5 vaccine, IgG levels peaked at 8 weeks post-immunization, whereas IgG responses in mice immunized with the BM vjbR::Tn5 with VpB in the shell, levels increased steadily and reached a maximum after 18 weeks post immunization. In this case, an induction of higher and sustained antibody levels correlated with enhanced protection for both BM vjbR::Tn5 in alginate and vjbR::Tn5 in VpB shell formulations. Mice vaccinated with the encapsulated vjbR::Tn5 revealed elevated secretion from spleen cells of INF-γ, IL-12, but no IL-4. These suggested an induction of a T helper 1 (Th1) response reflecting the enhanced immunity associated with microencapsulation (Arenas-Gamboa et al., 2008).
  • Challenge Protocol: At certian times after vaccination, mice were challenged IP using 1 x 10^5 CFU/mouse of B.melitensis wild-type 16M. One week post challenge, mice were euthanizediation and their spleens were removed .
  • Efficacy: A single immunization dose in BALB/c mice with the encapsulated vjbR mutant improved protection against wild-type B. melitensis 16M challenge compared to the nonencapsulated vaccine strain (P<0.05) .
  • Host Ifng (Interferon gamma) response
    • Description: Cytokine secretion from spleen cells of mice vaccinated with the encapsulated vjbR::Tn5 revealed significantly elevated secretion of gamma interferon compared to non-vaccinated mice 10 and 30 weeks post vaccination (Arenas-Gamboa et al., 2008).
    • Detailed Gene Information: Click Here.
  • Host Il12b response
    • Description: Cytokine secretion from spleen cells of mice vaccinated with the encapsulated vjbR::Tn5 revealed significantly elevated secretion of interleukin-12 compared to non-vaccinated mice 10 and 30 weeks post vaccination (Arenas-Gamboa et al., 2008).
    • Detailed Gene Information: Click Here.
References
Arenas-Gamboa et al., 2008: Arenas-Gamboa AM, Ficht TA, Kahl-McDonagh MM, Rice-Ficht AC. Immunization with a Single Dose of a Microencapsulated Brucella melitensis Mutant Enhances Protection Against Wild-type Challenge. Infection and immunity. 2008; ; . [PubMed: 18362129].