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Vaccine Detail

CVD 908-htrA
Vaccine Information
  • Vaccine Name: CVD 908-htrA
  • Target Pathogen: Salmonella spp.
  • Target Disease: Salmonellosis
  • Vaccine Ontology ID: VO_0002865
  • Type: Live, attenuated vaccine
  • Antigen: The antigen was htrA-deleted S.Typhi (Tacket and Levine, 2007).
  • AroC gene engineering:
    • Type: Recombinant protein preparation
    • Description: HtrA was deleted in Salmonella organisms, which created a mutant that was less virulent and more susceptible to oxidative killing. HtrA encodes a heat-shock protein in Salmonella (Tacket and Levine, 2007).

    • Detailed Gene Information: Click Here.
  • Preparation: Formation of CVD 908-htrA was conducted from original CVC 908, and the vaccine created consisted of live lyophilized organisms in single-dose glass vials to be resuspended in buffer solution (Tacket and Levine, 2007).
  • Virulence: CVD 908-htrA retained the immunogenicity of the parent CVD 908, but no vaccine bacteremias were detected among people who received a single dose of 5 × 107, 5 × 108, or 5 × 109 cfu, despite surveillance for bacteremias after vaccination. The immune responses measured by seroconversion rates with IgG anti-LPS after vaccination with CVD 908 and CVD 908-htrA were very similar. Most volunteers developed ASC responses, regardless of the vaccine strain received. Some lymphoproliferative responses to flagella and particulate antigen after CVD 908-htrA vaccination were also observed (Tacket and Levine, 2007).
Host Response

Human Response

  • Vaccination Protocol: In this study, 80 healthy adult outpatient volunteers were randomized to receive, with buffer, a single oral administration of high-dose CVD 908-htrA (4.5 × 108 cfu), lower-dose CVD 908-htrA (5 × 107 cfu), or placebo. On day 28, there was a crossover in which the volunteers who had ingested CVD 908-htrA vaccine on day 0 received placebo and those who had received placebo on day 0 received CVD 908-htrA vaccine in either the high or the lower dose (Tacket and Levine, 2007).
  • Side Effects: The incidence of adverse effects was the same in recipients of placebo, high-dose vaccine, or lower-dose vaccine after vaccination. Diarrhea, a potential concern observed in a small number of vaccine recipients in the uncontrolled, phase 1 study, occurred in 3 (4%) of 76 placebo recipients, 1 (3%) of 39 lower-dose vaccine recipients, and 4 (10%) of 39 high-dose vaccine recipients (a statistically insignificant difference). However, in a secondary analysis of the incidence of symptoms in the first 7 days after vaccination, recipients of the high-dose vaccine were found to be slightly more likely to have had diarrhea (8%) than were recipients of placebo (0%) (P = .04). No recipient of the lower-dose vaccine had diarrhea in the first 7 days after vaccination (Tacket and Levine, 2007).
  • 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].