• Vaccine Name: Recombinant Y. pestis YopD protein vaccine
• Target Pathogen: Yersinia pestis
• Target Disease: Plague
• Vaccine Ontology ID: VO_0000834
• Type: Subunit vaccine
• LcrV from Y. pestis CO92 gene engineering:
  • Type: Protein
  • Description:
  • Detailed Gene Information: Click Here.
• YopD from Y. pestis CO92 gene engineering:
  • Type: Protein
  • Description: Yop targeting negative regulator; translocon component; important for translocation pore formation.
  • Detailed Gene Information: Click Here.
• Adjuvant:
  • Adjuvant name:
  • VO adjuvant ID: VO_0001238
  • Description: R-730 emulsion (Ribi ImmunoChem Research, Inc., Hamilton, Mont.)(Andrews et al., 1999)
• Preparation: The yopD loci from Yersinia pestis was amplified by PCR, cloned, and expressed in Escherichia coli. The purified protein was mixed with an equal volume of the adjuvant to give a final protein concentration of 100 µg/ml (Andrews et al., 1999).
• Virulence:
• Description: Yersinia outer proteins (Yops) are virulence determinants synthesized by the Yersinia species pathogenic for humans, including Y. pestis, the causative agent of plague. The Yop proteins are encoded on a 75-kb plasmid, and in vitro expression from these genes, as well as subsequent secretion and translocation by a Type III secretion system, are regulated by temperature, calcium, and eukaryotic cell contact. There are various functions known for some of the Yops, including translocation and sensor functions in Yop B/D and Yop N. Previous studies showed that antibodies to some Yops are present in convalescent-phase serum from patients infected with Y. pestis, as well as in rodent serum after experimental Y. pestis infection, which suggests that Yops are antigenic. Vaccination with Yop-containing culture supernatants from growth-restricted Yersinia enterocolitica protected mice from a lethal intraperitoneal (i.p.) dose of virulent Y. pestis; however, interpretation is complicated by the likely presence of V antigen in the crude supernatants, as V is known to be a protective antigen (Andrews et al., 1999).

Mouse Response

• Host Strain: Female, 8-week-old, Hsd:ND4 Swiss Webster outbred mice (Harlan Sprague Dawley, Indianapolis, Ind.).
• Vaccination Protocol: Thirty micrograms of each Yop-adjuvant mixture was administered to two groups each of 8 to 14 mice, followed by one boost of 30 µg at 30 days post-primary vaccination. Mice in all groups were subsequently boosted with 30 µg of each antigen (15 µg s.c. and 15 µg i.p.) on day 60. A control group was vaccinated with the adjuvant R-730 emulsion alone (Anderson et al., 1996).
• Side Effects: None noted.
• Efficacy: YopD offered protection against challenge with the virulent, nonencapsulated C12, with a statistically significant increase in mean survival time (26.2+/-1.7 days, P < 0.001) in one experiment. In a second experiment, the mean survival time was again highly significant (22.4+/-3.1 days, P = 0.006). The overall average mean survival time was 28 days (Andrews et al., 1999). The ability of YopD to protect mice against nonencapsulated Y. pestis C12 strongly suggests that at least one of the Yops may be important in eliciting a protective immune response against lethal Y. pestis s.c. challenge. The failure of YopD to protect against encapsulated organisms as it protects against the nonencapsulated strain may result from a masking effect of the F1 capsule on secreted YopD, which blocks the antibody-antigen interaction at the surface of the bacterium. Experiments are currently being conducted to examine these hypotheses (Andrews et al., 1999).
• Description: Significant protection of mice against challenge with encapsulated CO92 was not observed in any of the Yops except YopD (Andrews et al., 1999).