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Vaccine Detail

CVD 1204(pGA1-CS2)
Vaccine Information
  • Vaccine Name: CVD 1204(pGA1-CS2)
  • Target Pathogen: Shigella
  • Target Disease: Shigellosis
  • Vaccine Ontology ID: VO_0000733
  • Type: Live, attenuated vaccine
  • AroA gene engineering:
    • Type: Recombinant protein preparation
    • Description:
    • Detailed Gene Information: Click Here.
  • Preparation: This vaccine is a recombinant Shigella flexneri 2a strain CVD 1204 that expresses either Enterotoxigenic Escherichia coli (ETEC) CS2 Fimbriae (Altboum et al., 2001). Vaccines were prepared containing approximately 2 X 10^9 CFU of bacteria per syringe. The bacteria were grown on TSA-Congo red-guanine plates and harvested in PBS (Altboum et al., 2001).
Host Response

Guinea pig Response

  • Vaccination Protocol: Guinea pigs were inoculated intranasally on days 1 and 15 with approximately 2 x 10^9 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 10^10 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: Following a single dose of any CVD 1204 inoculum, half of the animals responded with anti-Shigella LPS mucosal IgA, whereas three-fourths of the animals responded with anti-Shigella LPS serum IgG. All animals immunized with CVD 1204(pGA1-CS2) (groups 3 and 4) developed anti-CS2 mucosal IgA and serum IgG following a single dose. Two immunizations were required to elicit anti-CS2 serum IgG responses in all animals (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 10^8 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-CS2) had a score of 1 on day 3. 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).
  • Host IgA response
    • Description: Following a single dose of any CVD 1204 inoculum, half of the animals responded with anti-Shigella LPS mucosal IgA. After second immunization, the most dramatic difference in IgA titers between pre and post immunization was seen in guinea pigs (Altboum et al., 2001).
    • Detailed Gene Information: Click Here.
  • Host IgG Fc receptor II response
    • Description: Following a single dose of any CVD 1204 inoculum, three-fourths of the animals responded with anti-Shigella LPS serum IgG. A dramatic increase in IgG titers between pre and post immunized guinea pigs was seen after the second immunization (Altboum et al., 2001).
    • Detailed Gene Information: Click Here.
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].