Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1997 Nov;65(11):4476–4482. doi: 10.1128/iai.65.11.4476-4482.1997

Regions of Yersinia pestis V antigen that contribute to protection against plague identified by passive and active immunization.

J Hill 1, S E Leary 1, K F Griffin 1, E D Williamson 1, R W Titball 1
PMCID: PMC175643  PMID: 9353022

Abstract

V antigen of Yersinia pestis is a multifunctional protein that has been implicated as a protective antigen, a virulence factor, and a regulatory protein. A series of V-antigen truncates expressed as glutathione S-transferase (GST) fusion proteins (GST-V truncates) have been cloned and purified to support immunogenicity and functionality studies of V antigen. Immunization studies with GST-V truncates have identified two regions of V antigen that confer protection against Y. pestis 9B (a fully virulent human pneumonic plague isolate) in a mouse model for plague. A minor protective region is located from amino acids 2 to 135 (region I), and a major protective region is found between amino acids 135 and 275 (region II). In addition, analysis of IgG titers following immunization suggested that the major antigenic region of V antigen is located between amino acids 135 and 245. A panel of monoclonal antibodies raised against recombinant V antigen was characterized by Western blotting against GST-V truncates, and epitopes of most of the monoclonal antibodies were mapped to region I or II. Monoclonal antibody 7.3, which recognizes an epitope in region II, passively protected mice against challenge with 12 median lethal doses of Y. pestis GB, indicating that region II encodes a protective epitope. This is the first report of a V-antigen-specific monoclonal antibody that will protect mice against a fully virulent strain of Y. pestis. The combined approach of passive and active immunization has therefore confirmed the importance of the central region of the protein for protection and also identified a previously unknown protective region at the N terminus of V antigen.

Full Text

The Full Text of this article is available as a PDF (404.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andrews G. P., Heath D. G., Anderson G. W., Jr, Welkos S. L., Friedlander A. M. Fraction 1 capsular antigen (F1) purification from Yersinia pestis CO92 and from an Escherichia coli recombinant strain and efficacy against lethal plague challenge. Infect Immun. 1996 Jun;64(6):2180–2187. doi: 10.1128/iai.64.6.2180-2187.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bergman T., Håkansson S., Forsberg A., Norlander L., Macellaro A., Bäckman A., Bölin I., Wolf-Watz H. Analysis of the V antigen lcrGVH-yopBD operon of Yersinia pseudotuberculosis: evidence for a regulatory role of LcrH and LcrV. J Bacteriol. 1991 Mar;173(5):1607–1616. doi: 10.1128/jb.173.5.1607-1616.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cavanaugh D. C., Elisberg B. L., Llewellyn C. H., Marshall J. D., Jr, Rust J. H., Jr, Williams J. E., Meyer K. F. Plague immunization. V. Indirect evidence for the efficacy of plague vaccine. J Infect Dis. 1974 May;129(Suppl):S37–S40. doi: 10.1093/infdis/129.supplement_1.s37. [DOI] [PubMed] [Google Scholar]
  4. LAWTON W. D., ERDMAN R. L., SURGALLA M. J. BIOSYNTHESIS AND PURIFICATION OF V AND W ANTIGEN IN PASTEURELLA PESTIS. J Immunol. 1963 Aug;91:179–184. doi: 10.21236/ad0299868. [DOI] [PubMed] [Google Scholar]
  5. Leary S. E., Williamson E. D., Griffin K. F., Russell P., Eley S. M., Titball R. W. Active immunization with recombinant V antigen from Yersinia pestis protects mice against plague. Infect Immun. 1995 Aug;63(8):2854–2858. doi: 10.1128/iai.63.8.2854-2858.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Marshall J. D., Jr, Bartelloni P. J., Cavanaugh D. C., Kadull P. J., Meyer K. F. Plague immunization. II. Relation of adverse clinical reactions to multiple immunizations with killed vaccine. J Infect Dis. 1974 May;129(Suppl):S19–S25. doi: 10.1093/infdis/129.supplement_1.s19. [DOI] [PubMed] [Google Scholar]
  7. Meyer K. F., Cavanaugh D. C., Bartelloni P. J., Marshall J. D., Jr Plague immunization. I. Past and present trends. J Infect Dis. 1974 May;129(Suppl):S13–S18. doi: 10.1093/infdis/129.supplement_1.s13. [DOI] [PubMed] [Google Scholar]
  8. Meyer K. F. Effectiveness of live or killed plague vaccines in man. Bull World Health Organ. 1970;42(5):653–666. [PMC free article] [PubMed] [Google Scholar]
  9. Motin V. L., Nakajima R., Smirnov G. B., Brubaker R. R. Passive immunity to yersiniae mediated by anti-recombinant V antigen and protein A-V antigen fusion peptide. Infect Immun. 1994 Oct;62(10):4192–4201. doi: 10.1128/iai.62.10.4192-4201.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Motin V. L., Nedialkov Y. A., Brubaker R. R. V antigen-polyhistidine fusion peptide: binding to LcrH and active immunity against plague. Infect Immun. 1996 Oct;64(10):4313–4318. doi: 10.1128/iai.64.10.4313-4318.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Motin V. L., Pokrovskaya M. S., Telepnev M. V., Kutyrev V. V., Vidyaeva N. A., Filippov A. A., Smirnov G. B. The difference in the lcrV sequences between Y. pestis and Y. pseudotuberculosis and its application for characterization of Y. pseudotuberculosis strains. Microb Pathog. 1992 Mar;12(3):165–175. doi: 10.1016/0882-4010(92)90050-x. [DOI] [PubMed] [Google Scholar]
  12. Nakajima R., Brubaker R. R. Association between virulence of Yersinia pestis and suppression of gamma interferon and tumor necrosis factor alpha. Infect Immun. 1993 Jan;61(1):23–31. doi: 10.1128/iai.61.1.23-31.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Nakajima R., Motin V. L., Brubaker R. R. Suppression of cytokines in mice by protein A-V antigen fusion peptide and restoration of synthesis by active immunization. Infect Immun. 1995 Aug;63(8):3021–3029. doi: 10.1128/iai.63.8.3021-3029.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Oyston P. C., Williamson E. D., Leary S. E., Eley S. M., Griffin K. F., Titball R. W. Immunization with live recombinant Salmonella typhimurium aroA producing F1 antigen protects against plague. Infect Immun. 1995 Feb;63(2):563–568. doi: 10.1128/iai.63.2.563-568.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Perry R. D., Fetherston J. D. Yersinia pestis--etiologic agent of plague. Clin Microbiol Rev. 1997 Jan;10(1):35–66. doi: 10.1128/cmr.10.1.35. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Price S. B., Cowan C., Perry R. D., Straley S. C. The Yersinia pestis V antigen is a regulatory protein necessary for Ca2(+)-dependent growth and maximal expression of low-Ca2+ response virulence genes. J Bacteriol. 1991 Apr;173(8):2649–2657. doi: 10.1128/jb.173.8.2649-2657.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Price S. B., Leung K. Y., Barve S. S., Straley S. C. Molecular analysis of lcrGVH, the V antigen operon of Yersinia pestis. J Bacteriol. 1989 Oct;171(10):5646–5653. doi: 10.1128/jb.171.10.5646-5653.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Roggenkamp A., Geiger A. M., Leitritz L., Kessler A., Heesemann J. Passive immunity to infection with Yersinia spp. mediated by anti-recombinant V antigen is dependent on polymorphism of V antigen. Infect Immun. 1997 Feb;65(2):446–451. doi: 10.1128/iai.65.2.446-451.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Russell P., Eley S. M., Hibbs S. E., Manchee R. J., Stagg A. J., Titball R. W. A comparison of Plague vaccine, USP and EV76 vaccine induced protection against Yersinia pestis in a murine model. Vaccine. 1995 Nov;13(16):1551–1556. doi: 10.1016/0264-410x(95)00090-n. [DOI] [PubMed] [Google Scholar]
  20. Skrzypek E., Straley S. C. Differential effects of deletions in lcrV on secretion of V antigen, regulation of the low-Ca2+ response, and virulence of Yersinia pestis. J Bacteriol. 1995 May;177(9):2530–2542. doi: 10.1128/jb.177.9.2530-2542.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Snapper C. M., Finkelman F. D., Paul W. E. Differential regulation of IgG1 and IgE synthesis by interleukin 4. J Exp Med. 1988 Jan 1;167(1):183–196. doi: 10.1084/jem.167.1.183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Une T., Brubaker R. R. Roles of V antigen in promoting virulence and immunity in yersiniae. J Immunol. 1984 Oct;133(4):2226–2230. [PubMed] [Google Scholar]
  23. Williams R. C., Jr, Gewurz H., Quie P. G. Effects of fraction I from Yersinia pestis on phagocytosis in vitro. J Infect Dis. 1972 Sep;126(3):235–241. doi: 10.1093/infdis/126.3.235. [DOI] [PubMed] [Google Scholar]
  24. Williamson E. D., Eley S. M., Griffin K. F., Green M., Russell P., Leary S. E., Oyston P. C., Easterbrook T., Reddin K. M., Robinson A. A new improved sub-unit vaccine for plague: the basis of protection. FEMS Immunol Med Microbiol. 1995 Dec;12(3-4):223–230. doi: 10.1111/j.1574-695X.1995.tb00196.x. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES