• Vaccine Name: Yersinia PAV
• Target Pathogen: Yersinia pestis
• Target Disease: Plague
• Vaccine Ontology ID: VO_0000833
• Type: Subunit vaccine
• Adjuvant:
  • Adjuvant name:
  • VO adjuvant ID: VO_0001260
  • Description: TiterMax (Hunter’s TiterMax R-1; CytRx Corp., Norcross, Ga.) (Nakajima et al., 1995).
• Preparation: Fusion between the structural gene of staphylococcal protein A (PA) present on the vector plasmid pRIT5 and that of V antigen (LcrV) obtained from the lcr plasmid of Y. pseudotuberculosis resulted in the PA-V antigen peptide (PAV), encoded on pPAV13 carried by protease-deficient Escherichia coli BL21, which contained 305 N-terminal amino acids from PA plus 259 C-terminal amino acids from V antigen and could be purified to homogeneity in one step by immunoglobulin G affinity chromatography. Rabbit antibodies raised against one or more epitopes present within an internal portion of the V antigen domain of PAV have accounted for protection against experimental plague. PAV was diluted in phosphate buffer to 2 mg/ml and emulsified separately with an equal volume of the adjuvant (Nakajima et al., 1995).
• Virulence:

Mouse Response

• Host Strain: 5 to 6 weeks of age Female Swiss-Webster mice (Charles River Laboratories, Wilmington, MA).
• Vaccination Protocol: Mice received a primary immunization on day 0 consisting of 25 ml of emulsion (containing 25 mg of homogenous PA or PAV) and then identical booster immunizations were given on days 21 and 35. Adjuvant emulsified with an equal volume of phosphate buffer alone was also used as a negative control (Nakajima et al., 1995).
• Persistence: During immunization of mice with PAV, serum antibodies directed against highly purified recombinant V antigen became evident by week 4 and achieved a maximum titer (optical density of ~0.6) by week 6 (Nakajima et al., 1995).
• Immune Response: Injected PAV but not PA markedly suppressed TNF-a and IFN-g normally induced upon infection of control mice with avirulent lcrV or Lcr2 mutants of Y. pestis and promoted in vivo survival of these isolates as well as salmonellae and Listeria monocytogenes (Nakajima et al., 1995).
• Side Effects: No side effects noted.
• Challenge Protocol: It is established that an ~70-kb Lcr plasmid enables Yersinia pestis, the causative agent of bubonic plague, to multiply in focal necrotic lesions within visceral organs of mice by preventing net synthesis of the cytokines tumor necrosis factor alpha (TNF-a) and gamma interferon (IFN-g), thereby minimizing inflammation (Lcr1). Rabbit antiserum raised against cloned staphylococcal protein A-V antigen fusion peptide (PAV) is known to passively immunize mice against 10 minimum lethal doses of intravenously injected Lcr1 cells of Y. pestis. In this study, injected PAV suppressed TNF-a and IFN-g in mice challenged with avirulent V antigen deficient Y. pestis (lcrV or Lcr2) and promoted survival in vivo of these isolates. Active immunization of mice with PAV protected against 1,000 minimum lethal doses of intravenously injected Lcr1 cells of Y. pestis. The progressive necrosis provoked by Lcr1 cells of Y. pestis in visceral organs of nonimmunized mice was replaced after active immunization with PAV by massive infiltration of neutrophils and mononuclear cells (which generated protective granulomas indistinguishable from those formed against avirulent Lcr2 mutants in nonimmunized mice). Significant synthesis of TNF-a and IFN-g occurred in spleens of mice actively immunized with PAV after challenge with Lcr1 cells of Y. pestis. These findings suggest that V antigen contributes to disease by suppressing the normal inflammatory response (Nakajima et al., 1995).
• Efficacy: PAV but not PA provided absolute protection against 10 MLD of Y. pestis (Nakajima et al., 1995).