Protective Immunity Against Plague

  • Claire Cornelius
  • Olaf Schneewind
  • Deborah Anderson
  • Lauriane Quenee
Part of the Advances In Experimental Medicine And Biology book series (AEMB, volume 603)

Plague, an infectious disease that reached catastrophic proportions during three pandemics, continues to be a legitimate public health concern worldwide. Although antibiotic therapy for the causative agent Yersinia pestis is available, pharmaceutical supply limitations, multi-drug resistance from natural selection as well as malicious bioengineering are a reality. Consequently, plague vaccinology is a priority for biodefense research. Development of a multi-subunit vaccine with Fraction 1 and LcrV as protective antigens seems to be receiving the most attention. However, LcrV has been shown to cause immune suppression and Y. pestis mutants lacking F1 expression are thought to be fully virulent in nature and in animal experiments. The LcrV variant, rV10, retains the well documented protective antigenic properties of LcrV but with diminished inhibitory effects on the immune system. More research is required to examine the molecular mechanisms of vaccine protection afforded by surface protein antigens and to decipher the host mechanisms responsible for vaccine success.


Protective Immunity Protective Antigen Yersinia Enterocolitica Yersinia Pestis Pneumonic Plague 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Achtman, M., Zurth, K., Morelli, G., Torrea, G., Guiyoule, A. and Carniel, E. (1999) Yersinia pestis, the cause of plague, is a recently emerged clone of Yersinia pseudotuberculosis. Proc. Natl. Acad. Sci. USA 96, 14043-14048.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Anderson, G.W., Jr., Leary, S.E.C., Williamson, E.D., Titball, R.C., Welkos, S.C., Worsham, P.L. and Friedlander, A.M. (1996) Recombinant V antigen protects mice against pneumonic and bubonic plague caused by F1-capsule-positive and -negative strains of Yersinia pestis. Infect. Immun. 64, 4580-4585.PubMedPubMedCentralGoogle Scholar
  3. Andrews, G.P., Heath, D.G., Anderson, G.W, Jr., 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. Infect. Im-mun. 64, 2180-2187.Google Scholar
  4. Andrews, G.P., Strachan, S.T., Benner, G.E., Sample, A.K., Anderson, G.W. Jr., Adamovicz, J.J., Welkos, S.L., Pullen, J.K. and Friedlander, A.M. (1999) Protective efficacy of recombinant Yersinia outer proteins against bubonic plague caused by encapsulated and nonencapsulated Yersinia pestis. Infect. Immun. 67, 1533-1537.PubMedPubMedCentralGoogle Scholar
  5. Baker, E.E., Somer, H., Foster, L.W., Meyer, E. and Meyer, K.F. (1952) Studies on immuniza-tion against plague. I. The isolation and characterization of the soluble antigen of Pas-teurella pestis. J. Immunol. 68, 131-145.PubMedGoogle Scholar
  6. Benner, G.E., Andrews, G.P., Byrne, W.R., Strachan, S.D., Sample, A.K., Heath, D.G. and Friedlander, A.M. (1999) Immune response to Yersinia outer proteins and other Yersinia pestis antigens after experimental infection in mice. Infect. Immun. 67, 1922-1928.PubMedPubMedCentralGoogle Scholar
  7. Boyd, A.P., Grosdent, N., Totemeyer, S., Geuijen, C., Bleves, S., Iriarte, M., Lambermont, I., Octave, J-N. and Cornelis, G.R. (2000) Yersinia enterocolitica can deliver Yop proteins into a wide range of cell types, development of a delivery system for heterologous pro-teins. Eur. J. Cell Biol. 79, 659-671.CrossRefPubMedGoogle Scholar
  8. Brubaker, R. R. (2003) Interleukin-10 and the inhibition of innate immunity to yersiniae: roles of Yops and LcrV (V antigen). Infect. Immun. 71, 3673-3681.CrossRefPubMedPubMedCentralGoogle Scholar
  9. Brubaker, R.R. (1969) Mutation rate to nonpigmentation in Pasteurella pestis. Journal of bacteriology. 98(3), 1404-1406.PubMedPubMedCentralGoogle Scholar
  10. Burrows, T.W. (1957) Virulence of Pasteurella pestis. Nature 179, 1246-1247.CrossRefPubMedGoogle Scholar
  11. Burrows, T. W. (1963) Virulence of Pasteurella pestis and immunity to plague. Ergebn. Mik-robiol. 37, 59-113.Google Scholar
  12. Burrows, T.W. and Bacon, G.A. (1956) The basis of virulence in Pasteurella pestis, antigen determining virulence. Br. J. Exp. Pathol. 37, 481-493.PubMedPubMedCentralGoogle Scholar
  13. Burrows, T.W. and Bacon, G.A. (1958) The effect of loss of different virulence determinants on the virulence and immunogenicity of strains of Pasteurella pestis. Br. J. Exp. Pathol. 39, 278-291.PubMedPubMedCentralGoogle Scholar
  14. Cornelis, G. R. (1998) The Yersinia deadly kiss. J. Bacteriol. 180, 5495-5504.PubMedPubMedCentralGoogle Scholar
  15. Cornelis, G.R., Boland, A., Boyd, A.P., Geuijen, C., Iriarte, M., Neyt, C., Sory, M.-P and Stainier, I. (1998) The virulence plasmid of Yersinia, an antihost genome. Microbiol. Mol. Biol. Rev. 62, 1315-1352.PubMedPubMedCentralGoogle Scholar
  16. Crook, L.D. and Tempest, B. (1992) Plague, a clinical review of 27 cases. Arch. Intern. Med. 152, 1253-1256.CrossRefPubMedGoogle Scholar
  17. Davis, K.J., 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 (Cercopitheus aethiops). Arch. Pathol. Lab. Med. 120,156-163.PubMedGoogle Scholar
  18. DeBord K.L., 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.CrossRefPubMedPubMedCentralGoogle Scholar
  19. Deng, W., Burland, V., Plunkett, G.R., Boutin, A., Mayhew, G.F., Liss, P., Perna, N.T., Rose, D.J., Mau, B., Zhou, S., Schwartz, D.C., Fetherston, J.D., Lindler, L.E., Brubaker, R.R., Plano, G.V., Straley, S.C., McDonough, K.A., Nilles, M.L., Matson, J.S., Blattner, F.R. and Perry, R.D. (2002) Genome sequence of Yersinia pestis KIM. J. Bacteriol. 184, 4601-4611.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Eyles, J.E., Williamson, E.D., Spiers, I.D. and Alpar, H.O. (2000) Protection studies following bronchopulmonary and intramuscular immunization with yersinia pestis F1 and V subunit vaccines coencapsulated in biodegradable microspheres, a comparison of efficacy. Vaccine 18, 3266-3271.CrossRefPubMedGoogle Scholar
  21. Ferber, D.M. and Brubaker, R.R. (1981) Plasmids in Yersinia pestis. Infect. Immun. 31, 839-841.PubMedPubMedCentralGoogle Scholar
  22. Friedlander, A.M., Welkos, S.L., Worsham, P.L., Andrews, G.P., Heath, D.G., Anderson, G.W., Pitt, M.L.M., Estep, J. and Davis, K. Relationship between virulence and immunity as revealed in recent studies of the F1 capsule of Yersinia pestis. Clin. Infect. Dis. 21(Suppl. 2), 178-181.Google Scholar
  23. Galimand, M., Carniel, E. and Courvalin, P. (2006) Resistance of Yersinia pestis to antimicro-bial agents. Antimicrob Agents Chemother. 50, 3233-3236CrossRefPubMedPubMedCentralGoogle Scholar
  24. Galimand, M., Guiyoule, A., Gerbaud, G., Rasoamanana, B., Chanteau, S., Carniel, E. and Courvalin, P. (1997) Multidrug resistance in Yersinia pestis mediated by a transferable plasmid. N Engl J Med. 337:677-680.CrossRefPubMedGoogle Scholar
  25. Haffkine, W.M. (1897) Remarks on the plague prophylactic fluid. Br. Med. J. 1, 1461.CrossRefPubMedCentralGoogle Scholar
  26. Heath, D.G., Anderson, G.W., Jr., Mauro, J.M., Welkos, S.L., Andrews, G.P., Adamovicz, J.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.CrossRefPubMedGoogle Scholar
  27. Hu, P., Elliott, J., McCready, P., Skowronski, E., Garnes, J., Kobayashi, A., Brubaker, R. and Garcia, E. (1998) Structural organization of virulence-associated plasmids of Yersinia pestis. J. Bacteriol. 180, 5192-5202.PubMedPubMedCentralGoogle Scholar
  28. 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. JAMA 283, 2281-2290.CrossRefPubMedGoogle Scholar
  29. Jones, S.M., Day, F., Stagg, A.J. and Williamson, E.D. (2001) Protection conferred by a fully recombinant sub-unit vaccine against Yersinia pestis in male and female mice of four inbred strains. Vaccine. 19, 358-366.CrossRefGoogle Scholar
  30. Lawto, W.D., Erdman, R.L. and Surgalla, M.J. (1963) Biosynthesis and purification of V and W antigen in Pasteurella pestis. J. Immunol. 91, 179-184.Google Scholar
  31. Marketon, M.M., DePaolo, R.W., DeBord, K.L., Jabri, B. and Schneewind, O. (2005) Plague bacteria target immune cells during infection. Science. 309, 1739-1741.CrossRefPubMedPubMedCentralGoogle Scholar
  32. Meyer, K. (1961) Pneumonic plague. Bacteriol. Rev. 25, 249-261.PubMedPubMedCentralGoogle Scholar
  33. Meyer, K., Cavanaugh, D.C., Bartelloni, P.J. and Marshall, J.D. Jr. (1974) Plague Immuniza-tion I. Past and Present Trends. J. Infect. Dis. 129, S13-S18.CrossRefGoogle Scholar
  34. Meyer, K.F., Hightower, J.A. and McCrumb, F.R. (1974) Plague immunization. VI. Vaccina-tion with the fraction 1 antigen of Yersinia pestis. J. Infect. Dis. 129, S41-S45.CrossRefGoogle Scholar
  35. Michiels, T., Wattiau, P., Brasseur, R., Ruysschaert, J.-M and Cornelis, G. (1990) Secretion of Yop proteins by yersiniae. Infect. Immun. 58, 2840-2849.PubMedPubMedCentralGoogle Scholar
  36. Motin, V.L., Nedialkov, Y.A. and Brubaker, R.R. (1994) Passive immunity to yersiniae medi-ated by anti-recombinant V antigen and protein A-V antigen fusion peptide. Infect. Immun. 62, 3021-3029.Google Scholar
  37. Nakajima, R., Motin, V.L. and Brubaker, R.R. (1993) Association between virulence of Yersinia pestis and suppression of gamma interferon and tumor necrosis factor alpha. Infect. Immun. 63, 3021-3029.Google Scholar
  38. 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 by active immunization. Infect. Immun. 63, 3021-3029.PubMedPubMedCentralGoogle Scholar
  39. Nedialkov, Y.A., Motin, V.L. and Brubaker, R.R. (1997) Resistance to lipopolysaccharide mediated by the Yersinia pestis V antigen-polyhistidine fusion peptide, amplification of interleukin-10. Infect. Immun. 65, 1196-1203. PubMedPubMedCentralGoogle Scholar
  40. Overheim, K.A., Depaolo, R.W., Debord, K.L., Morrin, E.M., Anderson, D.M., Green, N.M., Brubaker, R.R., Jabri, B. and Schneewind, O. (2005) LcrV plague vaccine with altered immunomodulatory properties. Infect. Immun. 73, 5152-5159. CrossRefPubMedPubMedCentralGoogle Scholar
  41. Parkhill, J., Wren, B.W., Thompson, N.R., Titball, R.W., Holden, M.T., Prentice, M.B.,  Sebaihia, M., James, K.D., Churcher, C., Mungall, K.L., Baker, S., Dasham, D., Bentley, S.D., Brokks, K.Cerdeno-Tarraga, A.M., Chillingworth, T., Cronin, A., Davies, R.M., Davis, P., Dougan, G., Feltwell, T., Hamlin, N., Holroyd, S., Jagels, K., Karlyshev, A.V., Leather, S., Moule, S., Oyston, P.C., Quail, M., Rutherford, K., Simmonds, M., Skelton, J., Stevens, K., Whitehead, S. and Barrell, B.G. (2001) Genome sequence of Yersinia pestis, the causative agent of plague. Nature 413, 523-527. CrossRefPubMedGoogle Scholar
  42. Perry, R.D. and Fetherston, J.D. (1997) Yersinia pestis - etiologic agent of plague. Clin. Microbiol. Rev. 10, 35-66. PubMedPubMedCentralGoogle Scholar
  43. Philipovskiy, A.V., Cowan, C.R., Wulff-Strobel, S.H., 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. 73, 1532-1542. CrossRefPubMedPubMedCentralGoogle Scholar
  44. Prior J.L., Hitchen P.G., Williamson D.E., Reason A.J., Morris H.R., Dell A., Wren B.W., Titball R.W. (2001) Characterization of the lipopolysaccharide of Yersinia pestis. Microb. Pathog. 30, 49-57. CrossRefPubMedGoogle Scholar
  45. 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. CrossRefPubMedGoogle Scholar
  46. 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 macrophages is abrogated in IL-10-deficient mice. J. Immunol. 168, 1315-1321. CrossRefPubMedGoogle Scholar
  47. Sing, A., Rost, D., Tvardovaskaia, N., Roggenkamp, A., Wiedemann, A., Kirschning, C., Aepfelbacher, J.M. and Heesemann, J. (2002) Yersinia V-antigen exploits Toll-like receptor 2 and CD14 for interleukin 10-mediated immunosuppression. J. Exp. Med. 196, 1017-1024. CrossRefPubMedPubMedCentralGoogle Scholar
  48. Skurnik, M., Peippo, A. and Ervela, E. (2000) Characterization of the O-antigen gene clusters of Yersinia pseudotuberculosis and the cryptic O-antigen gene cluster of Yersinia pestis shows that the plague bacillus is most closely related to and has evolved from Y. pseudotuberculosis serotype O:1b. Mol. Microbiol. 37, 316-330. PubMedGoogle Scholar
  49. Taylor, V.L., Titball, R.W. and Oyston, P.C.F. (2005) Oral immunization with a dam mutant of Yersinia pseudotuberculosis protects against plague. Microbiol. 151, 1919-1926. CrossRefGoogle Scholar
  50. Titball, R.W. and Williamson, E.D. (2001) Vaccination against bubonic and pneumonic plague. Vaccine. 19, 4175-4184. CrossRefPubMedGoogle Scholar
  51. Une, T. and Brubaker, R.R. (1984) Role of V antigen in promoting virulence and immunity in yersiniae. J. Immunol. 133, 2226-2230. PubMedGoogle Scholar
  52. Weeks, S., Hill, J., Friedlander, A. and Welkos, A. (2002) Anti-V antigen antibody protects madcrophages from Yersinia pestis-induced cell death and promotes phagocytosis. Microb. Pathog. 32, 227-237. CrossRefPubMedGoogle Scholar
  53. (2006) Wkly. Epidemiol. Rec. 81, 278-84. Google Scholar
  54. Williamson, E.D (2001) Plague vaccine research and development. J. Appl. Microbiol. 91, 606-608. CrossRefPubMedGoogle Scholar
  55. Williamson, E.D., Eley, S.M., Stagg, A.J., Green, M., Russell, P. and Titball, R.W. (2000) A single dose sub-unit vaccine protects against pneumonic plague. Vaccine. 19, 566-571. CrossRefPubMedGoogle Scholar
  56. Williamson, E.D., 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 protects immunized animals against pneumonic plague. Vaccine. 15, 1079-1084. CrossRefPubMedGoogle Scholar
  57. Winter, C.C., Cherry, W.B. and Moody, M.D. (1960) An unusual strain of Pasteurella pestis isolated from a fatal case of human plague. Bull. W.H.O. 23, 408-409. PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Claire Cornelius
    • 1
  • Olaf Schneewind
    • 1
  • Deborah Anderson
    • 1
  • Lauriane Quenee
    • 1
  1. 1.Department of MicrobiologyUniversity of ChicagoChicagoUSA

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