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Yersinia pestis YadC: A Novel Vaccine Candidate Against Plague

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The Genus Yersinia

Part of the book series: Advances In Experimental Medicine And Biology ((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.

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References

  • Anderson, G.W., Jr., Worsham, P.L., Bolt, C.R., Andrews, G.P., Welkos, S.L., Friedlander, A.M. and Burans, J.P. (1997). Protection of mice from fatal bubonic and pneumonic plague by passive immunization with monoclonal antibodies against the F1 protein of Yersinia pestis. Am. J. Trop. Med. Hyg. 56, 571-573.

    Article  Google Scholar 

  • Andrews, G., Heath, D.G., Anderson, Jr., G.W., Welkos, S.L. and Friedlander, A.M. (1996). Fraction 1 capsular antigen (F1) purification from Yersinia pestis CO92 and from an Es-cherichia coli recombinant strain and efficacy against lethal plague challenge. Infec. Immun. 64, 2180-2187.

    CAS  Google Scholar 

  • Bendtsen, J.D., Nielsen, H., von Heijne, G. and Brunak, S. (2004). Improved detection of signal peptides: SignalP 3.0. J. Mol. Biol. 340: 783-795.

    Article  PubMed  Google Scholar 

  • Bosio, C., Goodyear, A.W. and Dow, S.W. (2005). Early interaction of Yersinia pestis with APCs in the lung. J. Immunol. 175, 6750-6756.

    Article  CAS  PubMed  Google Scholar 

  • British and US vaccine research groups. (2002). Abstracts O-35 and O-40, 8th International Symposium on Yersinia September 2002. Turky, Finland.

    Google Scholar 

  • Cotter, S., NSurana, N.K. and St. Geme III (2005). Trimeric autotransporters: a distinct subfamily of autotransporter proteins. Trends Microbiol. 13, 199-205.

    Article  CAS  PubMed  Google Scholar 

  • Cowan C., Philipovskiy, A.V., Wulff-Strobel, C.R., Ye, Z. and Straley, S.C. (2005). Anti-LcrV antibody inhibits delivery of Yops by Yersinia pestis KIM5 by directly promoting phagocytosis. Infect. Immun. 73, 6127-6137.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cowan, C., Jones, H.A., Kaya, Y.H., Perry, R.D. and Straley, S.C. (2000). Invasion of epithe-lial cells by Yersinia pestis: evidence for a Y. pestis-specific invasin. Infect. Immun. 68, 4523-4530.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Datsenko, K.A. and Wanner, B.L. (2000). One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. PNAS USA 97, 6640-6645.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Davis, K, Fritz, D.L., Pitt, M.L.M., Welkos, S.L., Worsham, P.L. and Friedlander, A.M. (1996). Pathology of experimental pneumonic plague produced by fraction 1-positive and fraction 1-negative Yersinia pestis in African green monkeys (Cercopithecus aethiops). Arch. Pathol. Lab. Med. 120, 156-163.

    CAS  PubMed  Google Scholar 

  • DeBord, K., Anderson, D.M., Marketon, M.M., Overheim, K.A., DePaolo, R.W., Ciletti, N.A., Jabri, B. and Schneewind, O. (2006). Immunogenicity and protective immunity against bubonic plague and pneumonic plague by immunization of mice with the recombinant V10 antigen, a variant of LcrV. Infect. Immun. 74, 4910-4914.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eyles, J., Spiers, I.D., Williamson, E.D. and Alpar, H.O. (1998). Analysis of local and sys-temic immunological responses after intra-tracheal, intra-nasal and intra-muscular admini-stration of microsphere co-encapsulated Yersinia pestis sub-unit vaccines. Vaccine 16, 2000-2009.

    Article  CAS  PubMed  Google Scholar 

  • Eyles, J., Elvin, S.J., Westwood, A., LeButt, C.S., Alpar, H.O., Somavarapu, S. and Williamson, E.D. (2004). Immunisation against plague by transcutaneous and intradermal application of subunit antigens. Vaccine 22, 4365-4373.

    Article  CAS  PubMed  Google Scholar 

  • Fields, K.A. and Straley, S.C. (1999). LcrV of Yersinia pestis enters infected eukaryotic cells by a virulence plasmid-independent mechanism. Infect. Immun. 67, 4801-4813.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Forman, S., Wulff, C.R., Perry, R.D. and Straley, S.C. (2006). Manuscript in preparation.

    Google Scholar 

  • Friedlander, A., Welkos, S.L., Worsham, P.L., Andrews, G.P., Heath, D.G., Anderson, Jr., G.W., Pitt, L.M., Estep, J. and Davis, K. (1995). The relationship between virulence and immunity as revealed in recent studies of the F1 capsule of Yersinia pestis. Clin. Infect. Dis. 21, 178-181.

    Article  Google Scholar 

  • Glynn, A., Roy, C.J., Powell, B.S., Adamovicz, J.J., Freytag, L.C. and Clements, J.D. (2005). Protection against aerosolized Yersinia pestis challenge following homologous and het-erologous prime-boost with recombinant plague antigens. Infect. Immun. 73, 5256-5261.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Glynn, A., Freytag, L.C. and Clements, J.D. (2005). Effect of homologous and heterologous prime-boost on the immune response to recombinant plague antigens. Vaccine 23, 1957-1965.

    Article  CAS  PubMed  Google Scholar 

  • Gruchalla, R.S. and Jones, J. (2003). Combating high-priority biological agents: what to do with drug-allergic patients and those for whom vaccination is contraindicated? J. Allergy Clin. Immunol. 112, 675-682.

    Article  PubMed  Google Scholar 

  • Heath, D., Anderson, Jr., G.W., Mauro, J.M., Welkos, S.L., Andrews, G.P., Adamovicz, J. and Friedlander, A.M. (1998). Protection against experimental bubonic and pneumonic plague by a recombinant capsular F1-V antigen fusion protein vaccine. Vaccine 16, 1131-1137.

    Article  CAS  PubMed  Google Scholar 

  • Hoiczyk, E., Roggenkamp, A., Reichenbecher, M., Lupas, A. and Heeseman, J. (2000). Struc-ture and sequence analysis of Yersinia YadA and Moraxella UspAs reveal a novel class of adhesins. EBMO J. 19, 5989-5999.

    CAS  Google Scholar 

  • Hudson, K., Bliska, J.B. and Bouton, A.H. (2005). Distinct mechanisms of integrin bindings by Yersinia pseudotuberculosis adhesins determine the phagocytic response of host macrophages. Cell. Microbiol. 7, 1471-1489.

    Article  Google Scholar 

  • Inglesby T.V., Dennis, D.T., Henderson, D.A., Bartlett, J.G., Ascher, M.S., Eitzen, E., Fine, A.D., Friedlander, A.M., Hauer, J., Koerner, J.F., Layton, M., McDade, J., Osterholm, M.T., O’Toole, T., Parker, G., Perl, T.M., Russell, P.K., Schoch-Spana, M. and Tonat, K. (2000). Plague as a biological weapon: Medical and public health management. Working Group on Civilian Biodefense. J. Am. Med. Assoc. 283, 2281-2290.

    Article  CAS  Google Scholar 

  • Lahteenmaki, K., Kukonen, M. and Korhonen, T.K. (2001). The Pla surface protease/adhesin of Yersinia pestis mediates bacterial invasion into human endothelial cells. FEBS Lett. 504, 69-72.

    Article  CAS  PubMed  Google Scholar 

  • Leary, S., Griffin, K.F., Garmory, H.S., Williamson, E.D. and Titball, R.W. (1997). Expres-sion of an F1/V fusion protein in attenuated Salmonella typhimurium and protection of mice against plague. Microb. Pathog. 23, 167-179.

    Article  CAS  PubMed  Google Scholar 

  • Marshall J.D., Jr., Bartelloni, P.J., Cavanaugh, D.C., Kadull, P.J. and Meyer, K.F. (1974). Plague immunization. II. relation of adverse clinical reactions to multiple immunizations with killed vaccine. J. Infect Dis. 129(Suppl), S19-S25.

    Article  Google Scholar 

  • Motin, V., Nakajima, R., Smirnov, G.B. and Brubaker, R.R. (1994). Passive immunity to yersiniae mediated by anti-recombinant V antigen and protein A-V antigen fusion peptide. Infect. Immun. 62, 4192-4201.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nakajima, R., Motin, V.L. and Brubaker, R.R. (1995). Suppression of cytokines in mice by protein A-V antigen fusion peptide and restoration of synthesis of active immunization. In-fect. Immun. 63, 3021-3029.

    CAS  Google Scholar 

  • Nakajima, R. and Burbaker, R.R. (1993). Association between virulence of Yersinia pestis and suppression of gamma interferon and tumor necrosis factor alpha. Infect. Immun. 61, 23-31.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nedialkov, Y., Motin, V.L. and Brubaker, R.R. (1997). Resistance to lipopolysaccharide mediated by the Yersinia pestis V antigen-polyhisitidine fusion peptide: amplification of interluekin-10. Infect. Immun. 65, 1196-1203.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nummelin H., Merckel, M.C., Leo, J.C., Lankinen, H., Skurnik, M. and Goldman, A. (2004). The Yersinia adhesin YadA collagen-binding domain structure is a novel left-handed par-allel beta-roll. EBMO J 23, 701-711.

    CAS  Google Scholar 

  • Perry, R. and Fetherston, J.D. (1997). Yersinia pestis--etiologic agent of plague. Clin. Micro-biol. Rev. 10, 35-66.

    CAS  Google Scholar 

  • Philipovskiy, A.V., Cowan, C., Wulff-Strobel, C.R., Burnett, S.H., Kerschen, E.J., Cohen, D.A., Kaplan, A.M. and Straley, S.C. (2005). Antibody against V antigen prevents Yopdependent growth of Yersinia pestis. Infect. Immun. 83, 1532-1542.

    Article  Google Scholar 

  • Roggenkamp A., Ackerman, N.A., Joacobi, C.A., Truelzsch, K., Hoffman, H. and Heeseman, J. (2003). Molecular analysis of transport and oligomerization of theYersinia enterocolitica adhensin YadA. J. Bacteriol. 185, 3735-3744.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Russell, P., Eley, S.M., Hibbs, S.E., Manchee, R.J., Stagg, A.J. and Titball, R.W. (1995). A comparison of plague vaccine, USP and EV76 vaccine induced protection against Yersinia pestis in a murine model. Vaccine 13, 1551-1556.

    Article  CAS  PubMed  Google Scholar 

  • Simpson, W., Thomas, R.E. and Schwan, T.G. (1990). Recombinant capsular antigen (fraction 1) from Yersinia pestis induces a protective antibody response in BALB/c mice. Am. J. Trop. Med. Hyg. 43, 389-396.

    Article  CAS  PubMed  Google Scholar 

  • Sing, A., Roggenkamp, A., Geiger, A.M. and Heesemann, J. (2002). Yersinia enterocolitica evasion of the host immune response by V antigen-induced IL-10 production of macro-phages is abrogated in IL-10-deficient mice. J. Immunol. 168, 1315-1321.

    Article  CAS  PubMed  Google Scholar 

  • Sing, A., Tvardovaskaia, N., Rost, D., Kirschning, C., Wagner, H. and Heesemann, J. (2003). Contribution of Toll-like receptors 2 and 4 in an oral Yersinia enterocolitica mouse infec-tion model. Int. J. Med. Microbiol. 293, 341-348.

    Article  CAS  PubMed  Google Scholar 

  • Sing, A., Tvardovskaia, N., Rost, D., Kirschning, C.J., Wagner, H. and Heeseman, J. (2003). Yersinia V-antigen exploits toll-like receptor 2 and CD14 for interleukin 10-mediated im-munosuppression. J. Exp. Med. 197, 1017-1024.

    Article  Google Scholar 

  • Straley, S.C. and Bowmer, W.S. (1986). Virulence genes regulated at the transcriptional level by Ca2- in Yersinia pestis include structural genes for outer membrane proteins. Infect. Immun. 51, 445-454.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Surgalla, M. and Beesley, E.D. (1969). Congo red-agar plating medium for detecting pigmen-tation in Pasturella pestis. Appl. Microbiol. 18, 834-837.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tahir E.Y. and Skurnik, M. (2001). YadA, the multifaceted Yersinia adhesin. Int. J. Med. Microbiol. 291, 209-218.

    Article  PubMed  Google Scholar 

  • Welkos, S., Davis, K.M., Pitt, L.M., Worsham, P.L. and Friedlander, A.M. (1995). Studies on the contribution of the F1 capsule-associated plasmid pFra to the virulence of Yersinia pestis. Contrib. Microbiol. Immunol. 13, 299-305.

    CAS  PubMed  Google Scholar 

  • Williamson, E., Flick-Smith, H.C., LeButt, C., Rowland, C.A., Jones, S.M., Waters, E.L., Gwyther, R.J., Miller, J., Packer, P.J. and Irving, M. (2005). Human immune response to a plague vaccine comprising recombinant F1 and V antigens. Infect. Immun. 2005, 3598-3608.

    Article  Google Scholar 

  • Williamson, E., Vessey, P.M., Gillhespy, K.J., Eley, S.M., Green, M. and Titball, R.W. (1999). An IgG1 titre to the F1 and V antigens correlates with protection against plague in the mouse model. Clin. Exp. Immunol. 116, 107-114.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Williamson, E., Eley, S.M., Stagg, A.J., Green, M., Russell, P. and Titball, R.W. (1997). A sub-unit vaccine elicits IgG in serum, spleen cell cultures and bronchial washings and pro-tects immunized animals against pneumonic plague. Vaccine 15, 1079-1084.

    Article  CAS  PubMed  Google Scholar 

  • Wulff-Strobel, C. R., Williams, A.W. and Straley, S.C. 2001. LcrQ and SycH function to-gether at the Ysc type III secretion system in Yersinia pestis to impose a hierarchy of se-cretion. Mol. Microbiol. 43, 411-423.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine, University of Kentucky, Lexington, KY, USA

    Brian S. Murphy

  2. Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, KY, USA

    Susan C. Straley, Beth A. Garvy & Christine R. Wulf

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  1. Brian S. Murphy
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  2. Susan C. Straley
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  3. Beth A. Garvy
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  1. University of Kentucky, 800 Rose Street, 40536, Lexington, KY, USA

    Robert D. Perry  & Jacqueline D. Fetherston  & 

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Murphy, B.S., Straley, S.C., Garvy, B.A., Wulf, C.R. (2007). Yersinia pestis YadC: A Novel Vaccine Candidate Against Plague. In: Perry, R.D., Fetherston, J.D. (eds) The Genus Yersinia. Advances In Experimental Medicine And Biology, vol 603. Springer, New York, NY. https://doi.org/10.1007/978-0-387-72124-8_37

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