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. 1997 May;65(5):1926–1930. doi: 10.1128/iai.65.5.1926-1930.1997

Expression of the Yersinia pestis capsular antigen (F1 antigen) on the surface of an aroA mutant of Salmonella typhimurium induces high levels of protection against plague.

R W Titball 1, A M Howells 1, P C Oyston 1, E D Williamson 1
PMCID: PMC175242  PMID: 9125581

Abstract

The caf operon from Yersinia pestis encoding the structural subunit (caf1), the molecular chaperone (caf1M), the outer membrane anchor (caf1A), and the regulatory protein (caf1R) was cloned into Salmonella typhimurium SL3261 aroA. The recombinant Salmonella organisms were encapsulated when cultured at 37 degrees C but not when cultured at 28 degrees C. Oral inoculation of mice with the recombinant Salmonella induced predominantly an immunoglobulin G2a response to F1 antigen, and isolated T cells showed a recall response to soluble or Salmonella-associated F1 antigen. Mice immunized with S. typhimurium SL3261 aroA expressing F1 antigen intracellularly developed lower antibody responses to F1 antigen and showed a T-cell recall response only to Salmonella-associated F1 antigen. Mice immunized orally with two doses of the recombinant Salmonella which expressed F1 antigen on the surface were protected against 10(7) 50% lethal doses (LD50) of virulent Y. pestis given by the subcutaneous route of challenge, whereas mice immunized with the recombinant Salmonella expressing F1 antigen intracellularly were only partially protected against 10(5) LD50 of Y. pestis.

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Selected References

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  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. BURROWS T. W., BACON G. A. The basis of virulence in Pasteurella pestis: the development of resistance to phagocytosis in vitro. Br J Exp Pathol. 1956 Jun;37(3):286–299. [PMC free article] [PubMed] [Google Scholar]
  3. Brett S. J., Dunlop L., Liew F. Y., Tite J. P. Influence of the antigen delivery system on immunoglobulin isotype selection and cytokine production in response to influenza A nucleoprotein. Immunology. 1993 Oct;80(2):306–312. [PMC free article] [PubMed] [Google Scholar]
  4. Charles I., Dougan G. Gene expression and the development of live enteric vaccines. Trends Biotechnol. 1990 May;8(5):117–121. doi: 10.1016/0167-7799(90)90151-m. [DOI] [PubMed] [Google Scholar]
  5. Cowling P., Moss P. Infectivity of pneumonic plague. BMJ. 1994 Nov 19;309(6965):1369–1369. doi: 10.1136/bmj.309.6965.1369a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cárdenas L., Clements J. D. Oral immunization using live attenuated Salmonella spp. as carriers of foreign antigens. Clin Microbiol Rev. 1992 Jul;5(3):328–342. doi: 10.1128/cmr.5.3.328. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. FOX E. N., HIGUCHI K. Synthesis of the fraction I antigenic protein by Pasteurella pestis. J Bacteriol. 1958 Feb;75(2):209–216. doi: 10.1128/jb.75.2.209-216.1958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fulop M., Manchee R., Titball R. Role of lipopolysaccharide and a major outer membrane protein from Francisella tularensis in the induction of immunity against tularemia. Vaccine. 1995 Sep;13(13):1220–1225. doi: 10.1016/0264-410x(95)00062-6. [DOI] [PubMed] [Google Scholar]
  9. Galyov E. E., Karlishev A. V., Chernovskaya T. V., Dolgikh D. A., Smirnov OYu, Volkovoy K. I., Abramov V. M., Zav'yalov V. P. Expression of the envelope antigen F1 of Yersinia pestis is mediated by the product of caf1M gene having homology with the chaperone protein PapD of Escherichia coli. FEBS Lett. 1991 Jul 29;286(1-2):79–82. doi: 10.1016/0014-5793(91)80945-y. [DOI] [PubMed] [Google Scholar]
  10. Galyov E. E., Smirnov OYu, Karlishev A. V., Volkovoy K. I., Denesyuk A. I., Nazimov I. V., Rubtsov K. S., Abramov V. M., Dalvadyanz S. M., Zav'yalov V. P. Nucleotide sequence of the Yersinia pestis gene encoding F1 antigen and the primary structure of the protein. Putative T and B cell epitopes. FEBS Lett. 1990 Dec 17;277(1-2):230–232. doi: 10.1016/0014-5793(90)80852-a. [DOI] [PubMed] [Google Scholar]
  11. Gupta R. K., Siber G. R. Method for quantitation of IgG subclass antibodies in mouse serum by enzyme-linked immunosorbent assay. J Immunol Methods. 1995 Apr 12;181(1):75–81. doi: 10.1016/0022-1759(94)00331-p. [DOI] [PubMed] [Google Scholar]
  12. Hess J., Gentschev I., Miko D., Welzel M., Ladel C., Goebel W., Kaufmann S. H. Superior efficacy of secreted over somatic antigen display in recombinant Salmonella vaccine induced protection against listeriosis. Proc Natl Acad Sci U S A. 1996 Feb 20;93(4):1458–1463. doi: 10.1073/pnas.93.4.1458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Karlyshev A. V., Galyov E. E., Abramov V. M., Zav'yalov V. P. Caf1R gene and its role in the regulation of capsule formation of Y. pestis. FEBS Lett. 1992 Jun 22;305(1):37–40. doi: 10.1016/0014-5793(92)80650-6. [DOI] [PubMed] [Google Scholar]
  14. Karlyshev A. V., Galyov E. E., Smirnov OYu, Guzayev A. P., Abramov V. M., Zav'yalov V. P. A new gene of the f1 operon of Y. pestis involved in the capsule biogenesis. FEBS Lett. 1992 Feb 3;297(1-2):77–80. doi: 10.1016/0014-5793(92)80331-a. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. 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]
  17. Meyer K. F., Hightower J. A., McCrumb F. R. Plague immunization. VI. Vaccination with the fraction I antigen of Yersinia pestis. J Infect Dis. 1974 May;129(Suppl):S41–S45. doi: 10.1093/infdis/129.supplement_1.s41. [DOI] [PubMed] [Google Scholar]
  18. Mosmann T. R., Coffman R. L. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol. 1989;7:145–173. doi: 10.1146/annurev.iy.07.040189.001045. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. 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]
  21. Simpson W. J., Thomas R. E., Schwan T. G. Recombinant capsular antigen (fraction 1) from Yersinia pestis induces a protective antibody response in BALB/c mice. Am J Trop Med Hyg. 1990 Oct;43(4):389–396. doi: 10.4269/ajtmh.1990.43.389. [DOI] [PubMed] [Google Scholar]
  22. Sjöstedt A., Sandström G., Tärnvik A. Immunization of mice with an attenuated Salmonella typhimurium strain expressing a membrane protein of Francisella tularensis. A model for identification of bacterial determinants relevant to the host defence against tularemia. Res Microbiol. 1990 Sep-Oct;141(7-8):887–891. doi: 10.1016/0923-2508(90)90126-b. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Stoker N. G., Fairweather N. F., Spratt B. G. Versatile low-copy-number plasmid vectors for cloning in Escherichia coli. Gene. 1982 Jun;18(3):335–341. doi: 10.1016/0378-1119(82)90172-x. [DOI] [PubMed] [Google Scholar]
  25. Thatte J., Rath S., Bal V. Immunization with live versus killed Salmonella typhimurium leads to the generation of an IFN-gamma-dominant versus an IL-4-dominant immune response. Int Immunol. 1993 Nov;5(11):1431–1436. doi: 10.1093/intimm/5.11.1431. [DOI] [PubMed] [Google Scholar]
  26. Williams J. E., Arntzen L., Tyndal G. L., Isaäcson M. Application of enzyme immunoassays for the confirmation of clinically suspect plague in Namibia, 1982. Bull World Health Organ. 1986;64(5):745–752. [PMC free article] [PubMed] [Google Scholar]
  27. 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]
  28. 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]

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