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Vaccine Comparison

S. dysenteriae 1 strain WRSd1 Shigella flexneri aroD mutant vaccine
Vaccine Information Vaccine Information
  • Vaccine Ontology ID: VO_0000676
  • Type: Live, attenuated vaccine
  • AroA gene engineering:
    • Type: Gene mutation
    • Description: WRSd1 was constructed from S. dysenteriae 1 strain 1617. The virG(icsA) deletion was constructed from a streptomycin-resistant mutant of 1617 by a filter mating procedures using a virG(icsA) deletion derivative, pvirG2. A colony that was invasive for HeLa cells and negative for the virG(icsA) gene by Southern blotting was grown anaerobically on plates containing chlorate for selection of resistant colonies that had lost the entire Shiga toxin gene. A virG(icsA) stxAB Str^r mutant selected from the chlorate plates was designated WRSd1 (Venkatesan et al., 2002).
    • Detailed Gene Information: Click Here.
  • Preparation: S. dysenteriae 1 strain WRSd1 is a attenuated vaccine that contains deletions of the virG(icsA) gene required for intercellular spreading and a 20-kb chromosomal region encompassing the Shiga toxin genes (stxAB) (Venkatesan et al., 2002). The vaccine was made with bacterial culture grown overnight on LB agar plates and harvested in PBS (Venkatesan et al., 2002).
  • Virulence: Attenuated
  • Description: Vaccination with WRSd1 conferred protection against challenge with each of three virulent S. dysenteriae 1 strains (Venkatesan et al., 2002).
  • Vaccine Ontology ID: VO_0002923
  • Type: Live, attenuated vaccine
  • Status: Research
  • Host Species as Laboratory Animal Model: Monkey
  • AroD gene engineering:
    • Type: Gene mutation
    • Description: This aroD mutant is from Shigella flexneri (Kärnell et al., 1993).
    • Detailed Gene Information: Click Here.
  • Immunization Route: Oral immunization
Host Response Host Response

Monkey Response

  • Host Strain: Rhesus (Macaca mulatta)
  • Vaccination Protocol: Five rhesus monkeys were a part of the study. 20 ml of saturated sodium bicarbonate was administered intragastrically through a pediatric stomach tube fitted over a disposable plastic syringe, followed by 20 ml
    of the bacterial inoculum (109 CFU) of WRSd1) in water. The inoculum was obtained by hydrating the lyophilized vaccine product (Venkatesan et al., 2002).
  • Persistence: Two of five monkeys excreted the vaccine strain in stool cultures for 48 h after the administration of the vaccine, as evidenced by transparent colonies on Hektoen agar plates (Venkatesan et al., 2002).
  • Immune Response: Four monkeys showed a 2-to 3-fold rise in serum immunoglobulin G (IgG) response to S. dysenteriae 1 LPS at day 7 or day 14 and one monkey showed a 3-fold rise in serum IgA responseto S. dysenteriae LPS. None of the monkeys had a detectable rectal lavage sample immune response (Venkatesan et al., 2002).
  • Side Effects: Not noted.
  • Challenge Protocol: Monkeys were challenged with 2 x 1010 CFU of SC602 vaccine (Venkatesan et al., 2002).
  • Efficacy: The immune response generated was higher than that observed in monkeys given 6 x 109 CFU of the cGMP product (Venkatesan et al., 2002).

Monkey Response

  • Persistence: An aroD mutant is highly attenuated in monkeys (Kärnell et al., 1993).
  • Efficacy: An aroD mutant induces significant protection in monkeys from challenge with wild type S. flexneri (Kärnell et al., 1993).

Guinea pig Response

  • Vaccination Protocol: The eyes of 12 guinea pigs were inoculated with 108 CFU of WRSd1. The eyes were observed for 5 to 6 days for evaluation of the Sereny reaction. When eyes were immunized for efficacy studies of vaccine candidates, mmunization was carried out twice at 2-week intervals (Venkatesan et al., 2002).
  • Immune Response: Not noted.
  • Side Effects: Side effects included purulence and conjunctivitis in some of the eyes tested (Venkatesan et al., 2002).
  • Challenge Protocol: Four weeks after the last immunization, animals were challenged at the same dose using one of three virulent S. dysenteriae 1 strains: 1617, the parent strain of WRSd1; Ubon 378; and Shiga (Venkatesan et al., 2002).
  • Efficacy: WRSd1 protected fully against challenge by Ubon 378 and Shiga. At the single dose used for immunization in this experiment, WRSd1 protected partially against the parent strain 1617 (Venkatesan et al., 2002).
References References
Venkatesan et al., 2002: Venkatesan MM, Hartman AB, Newland JW, Ivanova VS, Hale TL, McDonough M, Butterton J. Construction, characterization, and animal testing of WRSd1, a Shigella dysenteriae 1 vaccine. Infection and immunity. 2002; 70(6); 2950-2958. [PubMed: 12010984].
Kärnell et al., 1993: Kärnell A, Cam PD, Verma N, Lindberg AA. AroD deletion attenuates Shigella flexneri strain 2457T and makes it a safe and efficacious oral vaccine in monkeys. Vaccine. 1993; 11(8); 830-836. [PubMed: 8356844].