1887

Abstract

Vaccines which are efficacious against anthrax, such as the human vaccine, Anthrax Vaccine Absorbed (AVA), contain the protective antigen (PA) component of the anthrax toxins as the major protective immunogen. Although AVA protects against inhalational anthrax, the immune responses to and role in protection of PA and possibly other antigens have yet to be fully elucidated. Sera from animals immunized with a toxin-producing, unencapsulated live vaccine strain of have been reported to have anti-spore activities associated with the antitoxin humoral response. The authors performed studies to determine whether anti-PA antibody (Ab)-containing preparations stimulated spore uptake by phagocytes and suppressed the germination of spores . AVA- and PA-immune sera from several species enhanced the phagocytosis by murine peritoneal macrophages of spores of the virulent Ames and the Sterne vaccine strains. Antitoxin Abs appeared to contribute significantly, although not solely, to the enhanced uptake. Rabbit antisera to PA purified from either Sterne or a PA-producing pX01-cured recombinant, affinity-purified anti-PA IgG, and monkey antisera to AVA were used to assess the role of anti-PA Abs. Rabbit anti-PA Abs promoted the uptake of spores of the PA-producing strains Sterne, Ames and RP42, a mutant of Sterne producing only PA, but not of the pX01-ΔSterne-1 strain, ΔAmes strain, or RP4, a mutant of Sterne with deletions in the loci encoding PA and the oedema factor (EF) toxin component and producing only the lethal factor toxin component. Rabbit anti-PA and monkey anti-AVA Abs also significantly inhibited spore germination compared to preimmune serum or medium. Spore-associated proteins recognized by anti-PA Abs were detected by electron microscopy and confirmed by immunoblotting of spore coat extracts. Thus, the anti-PA Ab-specific immunity induced by AVA has anti-spore activity and might have a role in impeding the early stages of infection with spores.

Loading

Article metrics loading...

/content/journal/micro/10.1099/00221287-147-6-1677
2001-06-01
2019-10-23
Loading full text...

Full text loading...

/deliver/fulltext/micro/147/6/1471677a.html?itemId=/content/journal/micro/10.1099/00221287-147-6-1677&mimeType=html&fmt=ahah

References

  1. Aronson, A. I. & Fitz-James, P. ( 1976; ). Structure and morphogenesis of the bacterial spore coat. Bacteriol Rev 40, 360-402.
    [Google Scholar]
  2. Barnes, J. M. ( 1947; ). The development of anthrax following the administration of spores by inhalation. Br J Exp Pathol 28, 385.
    [Google Scholar]
  3. Beaman, T. C., Pankratz, H. S. & Gerhardt, P. ( 1971; ). Paracrystalline sheets reaggregated from solubilised exosporium of Bacillus cereus. J Bacteriol 107, 320-324.
    [Google Scholar]
  4. DesRosier, J. R. & Lara, J. C. ( 1984; ). Synthesis of the exosporium during sporulation of Bacillus cereus. J Gen Microbiol 103, 935-940.
    [Google Scholar]
  5. Dixon, T. C., Meselson, M., Guillemin, J. & Hanna, P. C. ( 1999; ). Anthrax. N Engl J Med 341, 815-826.[CrossRef]
    [Google Scholar]
  6. Dixon, T. C., Fadl, A. A., Koehler, T. M., Swanson, J. A. & Hanna, P. C. ( 2000; ). Early Bacillus anthracis–macrophage interactions: intracellular survival and escape. Cell Microbiol 2, 453-463.[CrossRef]
    [Google Scholar]
  7. Ezzell, J. W.Jr & Abshire, T. G. ( 1988; ). Immunological analysis of cell-associated antigens of Bacillus anthracis. Infect Immun 56, 349-356.
    [Google Scholar]
  8. Ezzell, J. S., Abshire, T. G. & Little, S. F. ( 1990; ). Identification of Bacillus anthracis by using monoclonal antibody to cell wall galactose-N-acetylglucosamine polysaccharide. J Clin Microbiol 28, 223-231.
    [Google Scholar]
  9. Fritz, D. L., Jaax, N. K., Lawrence, W. B., Davis, K. J., Pitt, M. L. M., Ezzell, J. W. & Friedlander, A. M. ( 1995; ). Pathology of experimental inhalation anthrax in the rhesus monkey. Lab Invest 73, 691-702.
    [Google Scholar]
  10. Gombas, D. & Labbe, R. ( 1981; ). Extraction of spore-lytic enzyme from Clostridium perfringens spores. J Gen Microbiol 126, 37-44.
    [Google Scholar]
  11. Guidi-Rontani, C., Weber-Levy, M., Labruyere, E. & Mock, M. ( 1999; ). Germination of Bacillus anthracis spores within alveolar macrophages. Mol Microbiol 31, 9-17.[CrossRef]
    [Google Scholar]
  12. Hanna, P. C. & Ireland, J. A. W. ( 1999; ). Understanding Bacillus anthracis pathogenesis. Trends Microbiol 7, 180-182.[CrossRef]
    [Google Scholar]
  13. Hansen, M. B., Nielsen, S. & Berg, K. ( 1989; ). Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill. J Immunol Methods 119, 203-210.[CrossRef]
    [Google Scholar]
  14. Ivins, B. E. & Welkos, S. L. ( 1986; ). Cloning and expression of the Bacillus anthracis protective antigen gene in Bacillus subtilis. Infect Immun 54, 537-542.
    [Google Scholar]
  15. Ivins, B. E., Fellows, P. F., Pitt, M. L. M., Estep, J. E., Welkos, S. L., Worsham, P. A. & Friedlander, A. M. (1996). Efficacy of a standard human anthrax vaccine against Bacillus anthracis aerosol spore challenge in rhesus monkeys. Salisbury Med Bull Suppl 87, 125–126.
  16. Leighton, T. J. & Doi, R. H. ( 1971; ). The stability of messenger ribonucleic acid during sporulation in Bacillus subtilis. J Biol Chem 246, 3189-3195.
    [Google Scholar]
  17. Levinson, H. S. & Hyatt, M. T. ( 1966; ). Sequence of events during Bacillus megaterium spore germination. J Bacteriol 91, 1811-1818.
    [Google Scholar]
  18. Lincoln, R. E., Rhian, M. A., Klein, F. & Fernelius, A. ( 1961; ). Pathogenesis as related to the physiological state of anthrax spores and cell. In Spores II , pp. 255-272. Edited by H. O. Halvorson. Minneapolis, MN:Burgess Publishing Co.
  19. Little, S. F. & Knudson, G. B. ( 1986; ). Comparative efficacy of Bacillus anthracis live spore vaccine and protective antigen vaccine against anthrax in the guinea pig. Infect Immun 52, 509-512.
    [Google Scholar]
  20. Little, S. F. & Lowe, J. R. ( 1991; ). Location of receptor-binding region of protective antigen from Bacillus anthracis. Biochem Biophys Res Commun 180, 531-537.[CrossRef]
    [Google Scholar]
  21. Little, S. F., Leppla, S. H. & Cora, E. ( 1988; ). Production and characterization of monoclonal antibodies to the protective antigen component of Bacillus anthracis toxin. Infect Immun 56, 1807-1813.
    [Google Scholar]
  22. Little, S. F., Novak, J. M., Lowe, J. R., Leppla, S. H., Singh, Y., Klimpel, K. R., Lidgerding, B. C. & Friedlander, A. M. ( 1996; ). Characterization of lethal factor binding and cell receptor binding domains of protective antigen of Bacillus anthracis using monoclonal antibodies. Infect Immun 56, 1807-1813.
    [Google Scholar]
  23. Little, S. F., Ivins, B. E., Fellows, P. F. & Friedlander, A. M. ( 1997; ). Passive protection by polyclonal antibodies against Bacillus anthracis infection in guinea pigs. Infect Immun 65, 5171-5175.
    [Google Scholar]
  24. Metchnikoff, E. (1905). Immunity in Infective Diseases. Cambridge: Cambridge University Press.
  25. Pepper, D. S. ( 1990; ). A user’s guide to protein A. In Laboratory Methods in Immunology , pp. 169-180. Edited by H. Zola. Boca Raton, FL:CRC Press.
  26. Pezard, C., Berche, P. & Mock, M. ( 1991; ). Contribution of individual toxin components to virulence of Bacillus anthracis. Infect Immun 59, 3472-3477.
    [Google Scholar]
  27. Pezard, C., Duflot, E. & Mock, M. ( 1993; ). Construction of Bacillus anthracis mutant strains producing a single toxin component. J Gen Microbiol 139, 2459-2463.[CrossRef]
    [Google Scholar]
  28. Pitt, M. L. M., Ivins, B. E., Estep, J. E., Farchaus, J. & Friedlander, A. M. ( 1996; ). Comparison of the efficacy of purified protective antigen and MDPH to protect non-human primates from inhalation anthrax. Salisbury Med Bull Suppl 87, 130.
    [Google Scholar]
  29. Pitt, M. L. M., Little, S., Ivins, B. E., Fellows, P. F., Boles, J., Barth, J., Hewetson, J. H. & Friedlander, A. M. ( 1999; ). In vitro correlate of immunity in an animal model of inhalational anthrax. J Appl Microbiol 87, 304.[CrossRef]
    [Google Scholar]
  30. Ross, J. M. ( 1957; ). The pathogenesis of anthrax following the administration of spores by the respiratory route. J Pathol Bacteriol 73, 485-494.[CrossRef]
    [Google Scholar]
  31. Stepanov, A. V., Marinin, L. I., Pomerantsev, A. P. & Staritsin, N. A. ( 1996; ). Development of novel vaccines against anthrax in man. J Biotechnol 44, 155-160.[CrossRef]
    [Google Scholar]
  32. Towbin, H., Staehelin, T. & Gordon, J. ( 1979; ). Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci USA 76, 4350-4354.[CrossRef]
    [Google Scholar]
  33. Vary, J. ( 1973; ). Germination of Bacillus megaterium spores after various extraction procedures. J Bacteriol 116, 797-802.
    [Google Scholar]
  34. Welkos, S. L., Trotter, R. W., Becker, D. M. & Nelson, G. O. ( 1989; ). Resistance to the Sterne strain of B. anthracis: phagocytic cell responses of resistant and susceptible mice. Microb Pathog 7, 15-36.[CrossRef]
    [Google Scholar]
  35. Worsham, P. L. & Sowers, M. R. ( 1999; ). Isolation of an asporogenic (spoOA) protective antigen-producing strain of Bacillus anthracis. Can J Microbiol 45, 1-8.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/00221287-147-6-1677
Loading
/content/journal/micro/10.1099/00221287-147-6-1677
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error