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Vaccine Detail

Aro-deleted S. Typhi
Vaccine Information
  • Vaccine Name: Aro-deleted S. Typhi
  • Target Pathogen: Salmonella spp.
  • Target Disease: Salmonellosis
  • Type: Live, attenuated vaccine
  • Antigen: The antigen used was aro-deleted S. Typhi, a strain designated as CVD 908 (Tacket and Levine, 2007).
  • AroD gene engineering:
    • Type: Recombinant protein preparation
    • Description: Inactivation of AroD results in attenuation, and the deletions of both AroC and AroD provide a high level of safety against restoration of pathogenicity by recombination. An aroC/aroD-deleted derivative of S. Typhi strain Ty2 (the parent strain of Ty21a) is designated the strain "CVD 908" (Tacket and Levine, 2007).
    • Detailed Gene Information: Click Here.
  • AroC gene engineering:
    • Type: Recombinant protein preparation
    • Description: Inactivation of AroC results in attenuation, and the deletions of both AroC and AroD provide a high level of safety against restoration of pathogenicity by recombination. An aroC/aroD-deleted derivative of S. Typhi strain Ty2 (the parent strain of Ty21a) is designated the strain "CVD 908" (Tacket and Levine, 2007).
    • Detailed Gene Information: Click Here.
  • Preparation: CVD 908 was created by deleting both aroC and aroD, preventing restoration of pathogenicity by recombination (Tacket and Levine, 2007).
  • Virulence: After a single dose of the vaccine (5 × 104 or 5 × 105 cfu), vaccine bacteremia was not detected in serial blood cultures. Half of the subjects tested with this dose developed serum IgG anti–lipopolysaccharide antibodies and IgA anti-LPS antibody-secreting cells (Tacket and Levine, 2007).
  • Description: The aromatic metabolites, such as aroC and aroD, force Salmonella to be nutritionally dependent on p-aminobenzoic acid and 2,3-dihydroxy, both of which are not available in mammilian tissues, preventing proliferation in the host cells (Tacket and Levine, 2007).
Host Response

Human Response

  • Vaccination Protocol: Each vaccine was ingested and contained 2.2 3 108 organisms of lyophilized vaccine. A second lower dose contained 5 3 107 viable organisms. Volunteers fasted for 90 minutes before and after vaccination. A placebo of sodium bicarbonate was also included (Tacket et al., 2000).
  • Immune Response: After a single oral dose, CVD 908-htrA stimulates vigor-
    ous mucosal, humoral, and cellular immune responses at levels (Tacket et al., 2000).
  • Side Effects: Two volunteers had diarrhea in the first 24 h after ingesting vaccine. Three volunteers had
    diarrhea that occurred later (Tacket et al., 2000).
  • Efficacy: Recipients of the high dose of CVD 908-htrA had a mean of 189 anti-LPS IgA ASC per 106 PBMC. Vigorous IgM and IgG ASC responses were detected among vaccinees. ASC-producing an-ti-H antigen IgA occurred in a majority of participants (Tacket et al., 2000).
  • Host IgA response
    • Description: ASCs producing IgA anti-LPS were detected in 100% of recipients of the high-dose vaccine and in 92% of recipients of the lower-dose vaccine. ASCs producing IgA anti-H antigen occurred in 79% and 73% of high- and lower-dose vaccine recipients, respectively (Tacket and Levine, 2007).
    • Detailed Gene Information: Click Here.
References
Tacket and Levine, 2007: Tacket CO, Levine MM. CVD 908, CVD 908-htrA, and CVD 909 live oral typhoid vaccines: a logical progression. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2007; 45 Suppl 1; S20-23. [PubMed: 17582563].
Tacket et al., 2000: Tacket CO, Sztein MB, Wasserman SS, Losonsky G, Kotloff KL, Wyant TL, Nataro JP, Edelman R, Perry J, Bedford P, Brown D, Chatfield S, Dougan G, Levine MM. Phase 2 clinical trial of attenuated Salmonella enterica serovar typhi oral live vector vaccine CVD 908-htrA in U.S. volunteers. Infection and immunity. 2000; 68(3); 1196-1201. [PubMed: 10678926].