Yersinia pestis YadC: A Novel Vaccine Candidate Against Plague

  • Brian S. Murphy
  • Susan C. Straley
  • Beth A. Garvy
  • Christine R. Wulf
Part of the Advances In Experimental Medicine And Biology book series (AEMB, volume 603)

Current subunit vaccines provide partial protection against pneumonic plague if the infecting Y. pestis strain is encapsulated (F1+). Here we describe YadC, a novel Y. pestis outer membrane protein that provides partial protection against a F1– Y. pestis strain. Swiss-Webster mice were immunized subcutaneously with glutathione S-transferase (GST) or His6-tagged (HT) purified fusion proteins (GST-YadC137-409 or HT-LcrV) or buffer emulsified with Alhydrogel. Intravenous challenge with 1 x 104 F1– Δpgm Y. pestis CO99-3015 revealed no protection for those mice immunized with GST-Alhydrogel alone, full protection for HT-LcrVimmunized mice, and partial protection for GST-YadC137-409 -immunized mice. Similarly, C57BL/6 mice were immunized with GST-YadC137-409, HT-LcrV, or GST all with Alhydrogel adjuvant. After intranasal challenge with 3 x 103 F1– Y. pestis CO99-3015, 87% of GSTYadC137- 409-immunized mice survived pneumonic plague. This is compared to the GST control group (0 surviving mice) and the LcrV-immunized group where 50% survived the challenge. This protection was correlated with a predominantly IgG1 response in LcrV-immunized mice and an IgG1/IgG3 antibody response in YadC-immunized mice. Additionally, we report the cytokine response from HT-LcrV- and GST-YadC137-409-stimulated peripherally derived macrophages. YadC-stimulated cells demonstrated a predominant pro-inflammatory cytokine production. This mixed Th1/Th2 response suggests that YadC’s protection may involve a different adaptive immune response than the LcrV protein that currently is part of plague vaccines.


Vaccine Candidate Partial Protection Yersinia Enterocolitica Yersinia Pestis Allelic Exchange 
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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Brian S. Murphy
    • 1
  • Susan C. Straley
    • 2
  • Beth A. Garvy
    • 2
  • Christine R. Wulf
    • 2
  1. 1.Department of Internal MedicineUniversity of KentuckyLexingtonUSA
  2. 2.Department of Microbiology, Immunology and Molecular GeneticsUniversity of KentuckyLexingtonUSA

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