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Vaccine Detail

G. lamblia bivalent DNA vaccine encoding a1-giardin and CWP2
Vaccine Information
  • Vaccine Name: G. lamblia bivalent DNA vaccine encoding a1-giardin and CWP2
  • Target Pathogen: Giardia lamblia
  • Type: Live, attenuated vaccine
  • Status: Research
  • Host Species for Licensed Use: Human
  • Antigen: a1-giardin - a1-giardin is a trophozoite structural protein that has shown promise as Giardia vaccine antigen candidates in murine models.(Radunovic et al., 2017)
    CWP2 - In past studies, results have indicated that Giardia has developed a classic repressor mechanism that allows encystation-specific control by the CWP2 promoter.The transmission-blocking vaccine induced reduction of cyst shedding attributes to the specific antibodies that target CWP2 and inhibit the formation of the cyst structure.(Abdul-Wahid and Faubert, 2007)
  • CWP2 gene engineering:
    • Type: DNA vaccine construction
    • Description: n past studies, results have indicated that Giardia has developed a classic repressor mechanism that allows encystation-specific control by the CWP2 promoter.The transmission-blocking vaccine induced reduction of cyst shedding attributes to the specific antibodies that target CWP2 and inhibit the formation of the cyst structure.(Abdul-Wahid and Faubert, 2007)
    • Detailed Gene Information: Click Here.
  • alpha1-giardin gene engineering:
    • Type: DNA vaccine construction
    • Description: a1-giardin is a trophozoite structural protein that has shown promise as Giardia vaccine antigen candidates in murine models.(Radunovic et al., 2017)
    • Detailed Gene Information: Click Here.
  • Adjuvant:
    • Adjuvant name:
    • VO adjuvant ID: VO_0000142
    • Description: IFA - Incomplete Freund's Adjuvant (IFA) is water-in-oil emulsion adjuvant that has been widely tested in humans where it was shown to augment antibody responses greater than other adjuvants. IFA mixed with or used in conjunction with other adjuvant-active compounds has proved successful in animal testing.(Jensen et al., 1998)
  • Adjuvant:
    • Adjuvant name:
    • VO adjuvant ID: VO_0000139
    • Description: Complete freund's adjuvant - CFA is a water-in-oil emulsion consisting of heat-killed Mycobacterium tuberculosis which helps induce immune responses greater than other adjuvants.
  • Immunization Route: oral
  • Description: This vaccine is a bivalent vaccine targeting a1-giardin and CWP2 which can protect mice against the colonization of Giardia trophozoite and Giardia infection (Feng et al., 2016).
Host Response

Mouse Response

  • Host Strain: BALB/c
  • Host age: 6-8 weeks
  • Host gender: Female
  • Vaccination Protocol: After one week quarantine, the mice were divided into five groups with 30 animals each. Each group of mice was inoculated orally with 1×105 bacteria of α1-giardin, CWP2-S, both α1-giardin and CWP2-S (each 1×105), SL7207/pVAX1 or PBS control in a total volume of 100 μl, respectively. All mice were fasted and only fed with water containing 1% sodium bicarbonate to neutralize stomach acidity overnight before inoculation. Mice were boosted with the same dose of bacteria 8 days after the first inoculation. Seven weeks after the boost, 10 mice from each group were euthanized by CO2 inhalation plus cervical dislocation to obtain blood samples, intestinal lavage fluid (ILF) and mesentery lymph nodes for immunological tests as described below.(Feng et al., 2016)
  • Immune Response: Intestinal lavage fluids were collected from vaccinated mice 7 weeks post-vaccination. Intestinal total IgA amounts were significantly increased in mice vaccinated with SL7207/-α1-giardin or pVAX1-CWP2 or both vaccines compared with those inoculated only with vector or PBS. The antigen-specific IgA levels were significantly higher in the intestinal mucos of mice immunized with a1-giardin, CWP2, and the a1-giardin+CWP2 vaccine. (Feng et al., 2016)
  • Challenge Protocol: The left 20 mice from each group were orally challenged with 1×105 trophozoites of G. lamblia C2 isolate in 100 μl TYI-S-33 medium. Four days after infection, ten mice from each group were sacrificed. The small intestine was removed and opened in 10 ml of ice-cold PBS for 10 min, and washed vigorously with 50 ml ice-cold PBS to detach trophozoites. The washed liquid was centrifuged at 800×g for 10 min and the pellets were suspended in 1 ml PBS. The Giardia trophozoites were counted under a phase-contrast microscope. Other ten infected mice from each group were maintained for collecting feces daily for consecutive 2 weeks. (Feng et al., 2016)
  • Efficacy: Compared to mice administrated with PBS alone, mice vaccinated with SL7207/pVAX1-α1-giardin obtained 74.2% trophozoite reduction in intestines 4 days post challenge and 28% reduction in the average cyst output in the feces during the two weeks post challenge with both statistical significance (p<0.01). Mice vaccinated with SL7207/pVAX1-CWP2 acquired only 10% reduction of trophozoites (p>0.05 compared to PBS group), however produced significant reduction of cyst shedding in the feces compared to PBS control (89%, p<0.01). When mice were co-vaccinated with SL7207/pVAX1-α1-giardin and SL7207/pVAX1-CWP2, a total of 79% reduction of trophozoite load in intestines and 93% reduction of cyst shedding in feces were obtained compared to the PBS control group with statistical significance (p<0.01)(Feng et al., 2016)
References