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Vaccine Detail

Recombinant SFL124-27 expressing S. dysenteriae type 1 O antigen
Vaccine Information
  • Vaccine Name: Recombinant SFL124-27 expressing S. dysenteriae type 1 O antigen
  • Target Pathogen: Shigella
  • Target Disease: Shigellosis
  • Vaccine Ontology ID: VO_0000674
  • Type: Recombinant vector vaccine
  • Preparation: S. flexneri SFL124-27 is a spontaneous rough mutant of the attenuated S. flexneri auxotrophic strain SFL124, which carries a deletion of the aroD gene. A recombinant strain SFL124-27 that expresses S. dysenteriae 1 O antigen was selected as the vaccine candidate (Klee et al., 1997).
  • Virulence: The vaccine was demonstrated to be immunogenic in animal models, leading to 47% full protection and 53% partial protection against challenge with the wild-type strain (Klee et al., 1997).
Host Response

Guinea pig Response

  • Host Strain: Dunkin Hartley
  • Vaccination Protocol: The Sereny test with guinea pigs was performed as follows: Congo red-positive colonies of the Shigella vaccine candidate were diluted in PBS, and 25 ml was applied to the conjunctival sacs of 15 adult Dunkin Hartley guinea pigs at days 0, 7, 14, and 21 with an average of four immunizing doses, 3.7 x 109 bacteria per eye (Klee et al., 1997).
  • Persistence: Vaccination led to statistically significant amounts of antibodies against S. Dysenteriae (Klee et al., 1997).
  • Immune Response: None of the four immunization doses given to the 15 guinea pigs resulted in detectable keratoconjunctivitis, thereby demonstrating the safety of this prototype vaccine candidate in this animal model (Klee et al., 1997).
  • Challenge Protocol: At day 35, the animals were challenged with 108 bacteria of the virulent strain S. dysenteriae 1 W30864 per eye, and the symptoms of keratoconjunctivitis were recorded for 6 days. As a control, another group of 14 nonvaccinated guinea pigs was also challenged with the virulent strain at day 35 (Klee et al., 1997).
  • Efficacy: In the vaccinated group, 7 of 15 animals developed no signs of keratoconjunctivitis (47% full protection), and in the other 8 animals, later development of the disease was observed (53% partial protection), resulting in a combined protection of 100%, whereas in the nonvaccinated group 71% of challenged animals rapidly developed severe disease.The vaccinated animals developed symptoms of keratoconjunctivitis later than animals of the control group, and the absolute number of guinea pigs showing strong reactions, or purulent inflammation of the whole eye, was significantly reduced (Klee et al., 1997).

Mouse Response

  • Host Strain: BALB/c
  • Vaccination Protocol: To assess whether the recombinant O antigen was immunogenic and to compare the immunogenicity with that of wild-type S. dysenteriae 1, groups of five six-week-old female BALB/c mice were immunized on days 0, 14, and 28 by intraperitoneal injection of 0.2 x 108 to 1.0 x 108 heat-killed bacteria suspended in PBS. Two weeks after the last immunization, the mice were sacrificed, blood samples were collected, and antibody titers against LPS of S. dysenteriae 1 were determined by enzyme-linked immunosorbent assay (Klee et al., 1997).
  • Persistence: The antibody titers of mice immunized with S. dysenteriae 1 or S. flexneri SFL124-27::Tn(rfp-rfb)-39 were significantly higher than the titers in the nonimmunized group and in mice immunized with the rough strain SFL124-27. This indicates the synthesis of enough surface-displayed LPS molecules to trigger a specific immune response, a prerequisite for a vaccine strain (Klee et al., 1997).
  • Challenge Protocol: No challenge was done on the mice, as this was only to assess the immunogenicity of the recombinant O antigen.
References
Klee et al., 1997: Klee SR, Tzschaschel BD, Fält I, Kärnell A, Lindberg AA, Timmis KN, Guzmán CA. Construction and characterization of a live attenuated vaccine candidate against Shigella dysenteriae type 1. Infection and immunity. 1997; 65(6); 2112-2118. [PubMed: 9169740].