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Infect Immun. 1996 June; 64(6): 2180–2187.
PMCID: PMC174053

Fraction 1 capsular antigen (F1) purification from Yersinia pestis CO92 and from an Escherichia coli recombinant strain and efficacy against lethal plague challenge.


As a first step in formulating an improved plague vaccine, we developed a simple purification strategy that produced high yields of pure cell-associated and culture supernatant-derived fraction 1 capsular antigen (F1) from both avirulent Yersinia pestis C092 (Pgm- Lcr-) and an Escherichia coli F1-producing recombinant strain. Cell-associated F1 was partially purified by sequential ammonium sulfate precipitations of a sodium chloride extract of acetone-dried bacteria harvested from broth cultures. Cell-free F1 was precipitated directly from culture supernatants with a single application of 30% ammonium sulfate. By exploiting the aggregative property of F1, large quantities of purified high-molecular-weight F1 species from both cell extracts and supernatants were isolated in the void volume of a preparative gel filtration column. Highly purified, endotoxin-free F1, combined with two different adjuvants, induced very high F1 titers in mice and protected them against either subcutaneous (70 to 100% survival) or aerosol (65 to 84% survival) challenge with virulent organisms. This protection was independent of the source of the antigen and the adjuvant used. F1-induced protection against both subcutaneous and aerosol challenge was also significantly better than that conferred by immunization with the licensed killed whole-cell vaccine. Our results indicate that F1 antigen represents a major protective component of previously studied crude capsule preparations, and immunity to F1 antigen provides a primary means for the host to overcome plague infection by either the subcutaneous or respiratory route.

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Selected References

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  • BAKER EE, SOMMER H, FOSTER LE, MEYER E, MEYER KF. Studies on immunization against plague. I. The isolation and characterization of the soluble antigen of Pasteurella pestis. J Immunol. 1952 Feb;68(2):131–145. [PubMed]
  • Bennett LG, Tornabene TG. Characterization of the antigenic subunits of the envelope protein of Yersinia pestis. J Bacteriol. 1974 Jan;117(1):48–55. [PMC free article] [PubMed]
  • Bolivar F, Rodriguez RL, Greene PJ, Betlach MC, Heyneker HL, Boyer HW, Crosa JH, Falkow S. Construction and characterization of new cloning vehicles. II. A multipurpose cloning system. Gene. 1977;2(2):95–113. [PubMed]
  • Cavanaugh DC, Elisberg BL, Llewellyn CH, Marshall JD, Jr, Rust JH, Jr, Williams JE, Meyer KF. Plague immunization. V. Indirect evidence for the efficacy of plague vaccine. J Infect Dis. 1974 May;129(Suppl):S37–S40. [PubMed]
  • Chen TH, Elberg SS. Scanning electron microscopic study of virulent Yersinia pestis and Yersinia pseudotuberculosis type 1. Infect Immun. 1977 Mar;15(3):972–977. [PMC free article] [PubMed]
  • EHRENKRANZ NJ, MEYER KF. Studies on immunization against plague. VIII. Study of three immunizing preparations in protecting primates against pneumonic plague. J Infect Dis. 1955 Mar-Apr;96(2):138–144. [PubMed]
  • ENGELSBERG E, LEVY JB. Studies on immunization against plague. VI. Growth of pasteurella pestis and the production of the envelope and other soluble antigens in a casein hydrolyzate mineral glucose medium. J Bacteriol. 1954 Apr;67(4):438–449. [PMC free article] [PubMed]
  • Galyov EE, Karlishev AV, Chernovskaya TV, Dolgikh DA, Smirnov OYu, Volkovoy KI, Abramov VM, Zav'yalov VP. 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. [PubMed]
  • Galyov EE, Smirnov OYu, Karlishev AV, Volkovoy KI, Denesyuk AI, Nazimov IV, Rubtsov KS, Abramov VM, Dalvadyanz SM, Zav'yalov VP. 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. [PubMed]
  • HIGUCHI K, SMITH JL. Studies on the nutrition and physiology of Pasteurella pestis. VI. A differential plating medium for the estimation of the mutation rate to avirulence. J Bacteriol. 1961 Apr;81:605–608. [PMC free article] [PubMed]
  • Karlyshev AV, Galyov EE, Abramov VM, Zav'yalov VP. Caf1R gene and its role in the regulation of capsule formation of Y. pestis. FEBS Lett. 1992 Jun 22;305(1):37–40. [PubMed]
  • Karlyshev AV, Galyov EE, Smirnov OYu, Guzayev AP, Abramov VM, Zav'yalov VP. 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. [PubMed]
  • LAWTON WD, FUKUI GM, SURGALLA MJ. Studies on the antigens of Pasteurella pestis and Pasteurella pseudotuberculosis. J Immunol. 1960 May;84:475–479. [PubMed]
  • Lee SF. Active release of bound antibody by Streptococcus mutans. Infect Immun. 1995 May;63(5):1940–1946. [PMC free article] [PubMed]
  • Martin DG, Jarvis FG, Milner KC. Physicochemical and biological properties of sonically treated Vi antigen. J Bacteriol. 1967 Nov;94(5):1411–1416. [PMC free article] [PubMed]
  • Meyer KF. Effectiveness of live or killed plague vaccines in man. Bull World Health Organ. 1970;42(5):653–666. [PubMed]
  • Meyer KF, Hightower JA, McCrumb FR. Plague immunization. VI. Vaccination with the fraction I antigen of Yersinia pestis. J Infect Dis. 1974 May;129(Suppl):S41–S45. [PubMed]
  • Oyston PC, Williamson ED, Leary SE, Eley SM, Griffin KF, Titball RW. Immunization with live recombinant Salmonella typhimurium aroA producing F1 antigen protects against plague. Infect Immun. 1995 Feb;63(2):563–568. [PMC free article] [PubMed]
  • Pautov VN, Chicherin Iu V, Evstigneev VI, Byvalov AA, Kedrov OA. Protektivnye svoistva fraktsii I chumnogo mikroba v éksperimente. Zh Mikrobiol Epidemiol Immunobiol. 1979 Oct;(10):37–42. [PubMed]
  • Simpson WJ, Thomas RE, Schwan TG. 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. [PubMed]
  • SPECK RS, WOLOCHOW H. Studies on the experimental epidemiology of respiratory infections. VIII. Experimental pneumonic plague in Macacus rhesus. J Infect Dis. 1957 Jan-Feb;100(1):58–69. [PubMed]
  • Surgalla MJ, Beesley ED. Congo red-agar plating medium for detecting pigmentation in Pasteurella pestis. Appl Microbiol. 1969 Nov;18(5):834–837. [PMC free article] [PubMed]
  • Tsai CM, Frasch CE. A sensitive silver stain for detecting lipopolysaccharides in polyacrylamide gels. Anal Biochem. 1982 Jan 1;119(1):115–119. [PubMed]
  • Vorontsov ED, Dubichev AG, Serdobintsev LN, Naumov AV. Association-dissociation processes and supermolecular organisation of the capsule antigen (protein F1) of Yersinia pestis. Biomed Sci. 1990 Apr;1(4):391–396. [PubMed]
  • Williams JE, Cavanaugh DC. Measuring the efficacy of vaccination in affording protection against plague. Bull World Health Organ. 1979;57(2):309–313. [PubMed]
  • Williams RC, Jr, Gewurz H, Quie PG. Effects of fraction I from Yersinia pestis on phagocytosis in vitro. J Infect Dis. 1972 Sep;126(3):235–241. [PubMed]
  • Zakrevskii VI, Plekhanova NG. Izuchenie protektivnykh svoistv antigensoderzhashchikh liposom razlichnogo lipidnogo sostava pri chume. Vestn Akad Med Nauk SSSR. 1990;(8):41–44. [PubMed]

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