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Vaccine Detail

SC602
Vaccine Information
  • Vaccine Name: SC602
  • Target Pathogen: Shigella
  • Target Disease: Shigellosis
  • Vaccine Ontology ID: VO_0000663
  • Type: Live, attenuated vaccine
  • Antigen: The antigen for this vaccine is Shigella flexneri 2a strain SC602 (Coster et al., 1999).
  • IcsA/VirG gene engineering:
    • Type: Recombinant protein preparation
    • Description: This SC602 vaccine was constructed with S. flexneri 2a strain 454 as the progenitor. The iuc mutation neccessary for producing SC602 was generated by recombination of iuc::Tn10 into the chromosome by using phage P1 transduction. Spontaneous excision of the tetracycline resistance gene, and its flanking regions including the iuc locus, was selected by growth on fusaric acid medium. The icsA gene was inactivated by double recombination with a kanamycin resistance-sucrose sensitivity cartridge carrying flanking regions of icsA. Deletion of the Kmr-sacB cartridge was selected by growth on sucrose, and the resistant clones were screened for retention of the invasive phenotype in HeLa cells. An isolate designated SC602 had suffered a deletion of the entire icsA gene along with substantial flanking sequences.This SC602 isolate was expanded into a master cell bank and was used in the vaccines (Coster et al., 1999).
    • Detailed Gene Information: Click Here.
  • Preparation: The Shigella flexneri 2a SC602 vaccine candidate carries deletions of the plasmid-borne virulence gene icsA (mediating intra- and intercellular spread) and the chromosomal locus iuc (encoding aerobactin).
  • Virulence: Attenuated.
Host Response

Human Response

  • Vaccination Protocol: Volunteers fasted for 90 minutes before and after vaccination. The inoculum was ingested by each volunteer 2 min after ingestion of 120 ml of the sodium bicarbonate solution. Placebo controls received sodium bicarbonate buffer with no added bacteria. SC602 dose selection studies. Thirty-three subjects were enrolled in the initial, placebo-controlled dose selection trial: eighteen subjects received the SC602 vaccine and fifteen received sodium bicarbonate placebo (Coster et al., 1999).
  • Persistence: Robust and prolonged intestinal colonization by S. flexneri 2a was observed in all volunteers who had ingested the SC602 vaccine. The peak excretion of vaccine was 104 to 106 CFU/g of stool regardless of the dose ingested (Coster et al., 1999).
  • Immune Response: Immune correlates of vaccine efficacy against diarrhea and severe shigellosis included a significant IgA ASC response and a threefold or greater rise in serum IgA antibody against S. flexneri 2a LPS. Other correlates of protection against all symptoms included urinary sIgA responses against 2a LPS in addition to IgG ASC and IgG serum responses. ASC levels peaked on day 7 and ELISA titers peaked on day 14 for vaccination(Coster et al., 1999).
  • Side Effects: Reportable intestinal symptoms included abdominal cramps, nausea, emesis, tenesmus, and gas. Constitutional symptoms in-
    cluded headache, myalgia, arthralgia, loss of appetite, and fatigue (Coster et al., 1999).
  • Challenge Protocol: The challenge inoculum, containing approximately 103 CFU of virulent S. flexneri 2a strain 2457T, was prepared and administered with sodium bicarbonate as described previously. All subjects
    who were vaccinated or challenged with S. flexneri were treated with ciprofloxacin (Coster et al., 1999).
  • Efficacy: SC602 gave significant protection against fever and severe shigellosis (Coster et al., 1999).
  • Host IgA response
    • Description: Immune correlates of vaccine efficacy against diarrhea and severe shigellosis included a significant IgA ASC response and a threefold or greater rise in serum IgA antibody against S. flexneri 2a LPS as compared to titers on day 0. Four of 12 vaccinees experienced a significant increase in IgA titers (Coster et al., 1999).
    • Detailed Gene Information: Click Here.
  • Host IgG response
    • Description: Correlates of protection against all symptoms included IgG ASC and IgG serum responses. A majority of volunteers had IgG anti-Ipa responses. Antibody titers were compared to day 0 titers (Coster et al., 1999).
    • Detailed Gene Information: Click Here.
References
Coster et al., 1999: Coster TS, Hoge CW, VanDeVerg LL, Hartman AB, Oaks EV, Venkatesan MM, Cohen D, Robin G, Fontaine-Thompson A, Sansonetti PJ, Hale TL. Vaccination against shigellosis with attenuated Shigella flexneri 2a strain SC602. Infection and immunity. 1999; 67(7); 3437-3443. [PubMed: 10377124].