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Vaccine Detail

CVD 1204(pGA1-CS3)
Vaccine Information
  • Vaccine Name: CVD 1204(pGA1-CS3)
  • Target Pathogen: Shigella
  • Target Disease: Shigellosis
  • Vaccine Ontology ID: VO_0000734
  • Type: Live, attenuated vaccine
  • Status: Licensed
  • Preparation: This vaccine is a recombinant Shigella flexneri 2a strain CVD 1204 that expresses either Enterotoxigenic Escherichia coli (ETEC) ETEC CS3 Fimbriae (Altboum et al., 2001). Vaccines were prepared containing approximately 2 X 109 CFU of bacteria per syringe. The bacteria were grown on TSA-Congo red-guanine plates and harvested in PBS (Altboum et al., 2001).
  • Immunization Route: Intramuscular injection (i.m.)
Host Response

Guinea pig Response

  • Vaccination Protocol: Guinea pigs were inoculated intranasally on days 1 and 15 with approximately 2 x 109 CFU of bacteria. Five groups of animals were inoculated: group 1 was immunized with CVD 1204; group 2 received CVD 1204-CS3; group 3 received CVD 1204-CS2; group 4 received a mixture of CVD 1204-CS3 plus CVD 1204-CS2; and group 5, serving as a placebo control, received 2 x 1010 CFU of E. coli HS. Groups 1 to 4 contained 5 animals each, whereas group 5 had 15 guinea pigs. Sera were obtained on days 0, 14, and 30 by anterior vena cava puncture of anesthetized animals. Tears were collected on the same days by lacrimal stimulation (Altboum et al., 2001).
  • Persistence: CVD 1204-CS3 or CVD 1204-CS3 and CVD 1204-CS2 mixed yielded titers that were boosted to even higher levels following the second dose. Antifimbrial titers were comparable in groups receiving a single strain or a mixture of strains Anti-CS3 IgG titers ranged in group 2 from 51,200 to 204,800 and in group 4 from 12,800 to 204,800. Anti-CS2 IgGtiters ranged in group 3 from 100 to 1,600 and in group 4 from 100 to 1,600. Anti-Shigella LPS IgG titers ranged in group 1 from 400 to 1,600, in group 2 from 800 to 3,200, in group 3 from 400 to 3,200, and in group 4 from 100 to 200 (Altboum et al., 2001).
  • Immune Response: Animals immunized with Shigella expressing CS3 developed serum antibodies that agglutinated Shigella as well as an ETEC strain bearing the homologous fimbriae (Altboum et al., 2001).
  • Side Effects: Conjuntivitis (Altboum et al., 2001).
  • Challenge Protocol: The guinea pigs were challenged 21 days following the second dose with 10 micoliters containing 108 CFU of wild-type S. flexneri 2a 2457T in the conjunctival sac (Altboum et al., 2001).
  • Efficacy: Upon Sereny test challenge with wild-type S. flexneri 2a, all 15 animals vaccinated intranasally with the placebo strain of E. coli HS developed severe keratoconjunctivitis. In contrast, none of the animals (5 per group) immunized with either native CVD 1204 or CVD 1204 expressing ETEC fimbriae developed severe keratoconjunctivitis (P < 0.01). One animal in the group immunized with CVD 1204(pGA1-CS3) had a score of 2 on days 3 and 4 (Altboum et al., 2001).
References
Altboum et al., 2001: Altboum Z, Barry EM, Losonsky G, Galen JE, Levine MM. Attenuated Shigella flexneri 2a Delta guaBA strain CVD 1204 expressing enterotoxigenic Escherichia coli (ETEC) CS2 and CS3 fimbriae as a live mucosal vaccine against Shigella and ETEC infection. Infection and immunity. 2001; 69(5); 3150-3158. [PubMed: 11292735].