1887

Abstract

Current vaccine approaches to combat anthrax are effective; however, they target only a single protein [the protective antigen (PA) toxin component] that is produced after spore germination. PA production is subsequently increased during later vegetative cell proliferation. Accordingly, several aspects of the vaccine strategy could be improved. The inclusion of spore-specific antigens with PA could potentially induce protection to initial stages of the disease. Moreover, adding other epitopes to the current vaccine strategy will decrease the likelihood of encountering a strain of (emerging or engineered) that is refractory to the vaccine. Adding recombinant spore-surface antigens (e.g. BclA, ExsFA/BxpB and p5303) to PA has been shown to augment protection afforded by the latter using a challenge model employing immunosuppressed mice challenged with spores derived from the attenuated Sterne strain of . This report demonstrated similar augmentation utilizing guinea pigs or mice challenged with spores of the fully virulent Ames strain or a non-toxigenic but encapsulated ΔAmes strain of , respectively. Additionally, it was shown that immune interference did not occur if optimal amounts of antigen were administered. By administering the toxin and spore-based immunogens simultaneously, a significant adjuvant effect was also observed in some cases. Thus, these data further support the inclusion of recombinant spore antigens in next-generation anthrax vaccine strategies.

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2012-10-01
2020-07-03
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References

  1. Baillie L., Townend T., Walker N., Eriksson U., Williamson D. 2004; Characterization of the human immune response to the UK anthrax vaccine. FEMS Immunol Med Microbiol 42:267–270 [CrossRef][PubMed]
    [Google Scholar]
  2. Basu S., Kang T. J., Chen W. H., Fenton M. J., Baillie L., Hibbs S., Cross A. S. 2007; Role of Bacillus anthracis spore structures in macrophage cytokine responses. Infect Immun 75:2351–2358 [CrossRef][PubMed]
    [Google Scholar]
  3. Beedham R. J., Turnbull P. C., Williamson E. D. 2001; Passive transfer of protection against Bacillus anthracis infection in a murine model. Vaccine 19:4409–4416 [CrossRef]
    [Google Scholar]
  4. Bielinska A. U., Janczak K. W., Landers J. J., Makidon P., Sower L. E., Peterson J. W., Baker J. R. Jr 2007; Mucosal immunization with a novel nanoemulsion-based recombinant anthrax protective antigen vaccine protects against Bacillus anthracis spore challenge. Infect Immun 75:4020–4029 [CrossRef][PubMed]
    [Google Scholar]
  5. Boyaka P. N., Tafaro A., Fischer R., Leppla S. H., Fujihashi K., McGhee J. R. 2003; Effective mucosal immunity to anthrax: neutralizing antibodies and Th cell responses following nasal immunization with protective antigen. J Immunol 170:5636–5643[PubMed] [CrossRef]
    [Google Scholar]
  6. Bozue J., Cote C. K., Moody K. L., Welkos S. L. 2007a; Fully virulent Bacillus anthracis does not require the immunodominant protein BclA for pathogenesis. Infect Immun 75:508–511 [CrossRef][PubMed]
    [Google Scholar]
  7. Bozue J., Moody K. L., Cote C. K., Stiles B. G., Friedlander A. M., Welkos S. L., Hale M. L. 2007b; Bacillus anthracis spores of the bclA mutant exhibit increased adherence to epithelial cells, fibroblasts, and endothelial cells but not to macrophages. Infect Immun 75:4498–4505 [CrossRef][PubMed]
    [Google Scholar]
  8. Brahmbhatt T. N., Darnell S. C., Carvalho H. M., Sanz P., Kang T. J., Bull R. L., Rasmussen S. B., Cross A. S., O’Brien A. D. 2007; Recombinant exosporium protein BclA of Bacillus anthracis is effective as a booster for mice primed with suboptimal amounts of protective antigen. Infect Immun 75:5240–5247 [CrossRef][PubMed]
    [Google Scholar]
  9. Brossier F., Levy M., Mock M. 2002; Anthrax spores make an essential contribution to vaccine efficacy. Infect Immun 70:661–664[PubMed]
    [Google Scholar]
  10. Cote C. K., Rossi C. A., Kang A. S., Morrow P. R., Lee J. S., Welkos S. L. 2005; The detection of protective antigen (PA) associated with spores of Bacillus anthracis and the effects of anti-PA antibodies on spore germination and macrophage interactions. Microb Pathog 38:209–225 [CrossRef][PubMed]
    [Google Scholar]
  11. Cote C. K., Van Rooijen N., Welkos S. L. 2006; Roles of macrophages and neutrophils in the early host response to Bacillus anthracis spores in a mouse model of infection. Infect Immun 74:469–480 [CrossRef][PubMed]
    [Google Scholar]
  12. Cote C. K., Bozue J., Moody K. L., DiMezzo T. L., Chapman C. E., Welkos S. L. 2008; Analysis of a novel spore antigen in Bacillus anthracis that contributes to spore opsonization. Microbiology 154:619–632 [CrossRef][PubMed]
    [Google Scholar]
  13. Cote C. K., Bozue J., Twenhafel N., Welkos S. L. 2009; Effects of altering the germination potential of Bacillus anthracis spores by exogenous means in a mouse model. J Med Microbiol 58:816–825 [CrossRef][PubMed]
    [Google Scholar]
  14. Cote C. K., Welkos S. L., Bozue J. 2011; Key aspects of the molecular and cellular basis of inhalational anthrax. Microbes Infect 13:1146–1155 [CrossRef][PubMed]
    [Google Scholar]
  15. Cybulski R. J. Jr, Sanz P., McDaniel D., Darnell S., Bull R. L., O’Brien A. D. 2008; Recombinant Bacillus anthracis spore proteins enhance protection of mice primed with suboptimal amounts of protective antigen. Vaccine 26:4927–4939 [CrossRef][PubMed]
    [Google Scholar]
  16. Dixon T. C., Meselson M., Guillemin J., Hanna P. C. 1999; Anthrax. N Engl J Med 341:815–826 [CrossRef][PubMed]
    [Google Scholar]
  17. Enkhtuya J., Kawamoto K., Kobayashi Y., Uchida I., Rana N., Makino S. 2006; Significant passive protective effect against anthrax by antibody to Bacillus anthracis inactivated spores that lack two virulence plasmids. Microbiology 152:3103–3110 [CrossRef][PubMed]
    [Google Scholar]
  18. Flick-Smith H. C., Waters E. L., Walker N. J., Miller J., Stagg A. J., Green M., Williamson E. D. 2005; Mouse model characterisation for anthrax vaccine development: comparison of one inbred and one outbred mouse strain. Microb Pathog 38:33–40 [CrossRef][PubMed]
    [Google Scholar]
  19. Fox C. B. 2009; Squalene emulsions for parenteral vaccine and drug delivery. Molecules 14:3286–3312 [CrossRef]
    [Google Scholar]
  20. Friedlander A. M. 1999; Clinical aspects, diagnosis and treatment of anthrax. J Appl Microbiol 87:303 [CrossRef][PubMed]
    [Google Scholar]
  21. Friedlander A. M. 2000; Anthrax: clinical features, pathogenesis, and potential biological warfare threat. Curr Clin Top Infect Dis 20:335–349[PubMed]
    [Google Scholar]
  22. Friedlander A. M., Pittman P. R., Parker G. W. 1999; Anthrax vaccine: evidence for safety and efficacy against inhalational anthrax. JAMA 282:2104–2106 [CrossRef][PubMed]
    [Google Scholar]
  23. Gauthier Y. P., Tournier J. N., Paucod J. C., Corre J. P., Mock M., Goossens P. L., Vidal D. R. 2009; Efficacy of a vaccine based on protective antigen and killed spores against experimental inhalational anthrax. Infect Immun 77:1197–1207 [CrossRef][PubMed]
    [Google Scholar]
  24. Glomski I. J., Corre J. P., Mock M., Goossens P. L. 2007a; Cutting edge: IFN-γ-producing CD4 T lymphocytes mediate spore-induced immunity to capsulated Bacillus anthracis . J Immunol 178:2646–2650[PubMed] [CrossRef]
    [Google Scholar]
  25. Glomski I. J., Piris-Gimenez A., Huerre M., Mock M., Goossens P. L. 2007b; Primary involvement of pharynx and Peyer’s patch in inhalational and intestinal anthrax. PLoS Pathog 3:e76 [CrossRef][PubMed]
    [Google Scholar]
  26. Goossens P. L., Sylvestre P., Mock M. 2007; Of spore opsonization and passive protection against anthrax. Microbiology 153:301–302, discussion 302–304 [CrossRef][PubMed]
    [Google Scholar]
  27. Hahn U. K., Boehm R., Beyer W. 2006; DNA vaccination against anthrax in mice—combination of anti-spore and anti-toxin components. Vaccine 24:4569–4571 [CrossRef][PubMed]
    [Google Scholar]
  28. Heine H. S., Bassett J., Miller L., Hartings J. M., Ivins B. E., Pitt M. L., Fritz D., Norris S. L., Byrne W. R. 2007; Determination of antibiotic efficacy against Bacillus anthracis in a mouse aerosol challenge model. Antimicrob Agents Chemother 51:1373–1379 [CrossRef][PubMed]
    [Google Scholar]
  29. Heninger S., Drysdale M., Lovchik J., Hutt J., Lipscomb M. F., Koehler T. M., Lyons C. R. 2006; Toxin-deficient mutants of Bacillus anthracis are lethal in a murine model for pulmonary anthrax. Infect Immun 74:6067–6074 [CrossRef][PubMed]
    [Google Scholar]
  30. Kudva I. T., Griffin R. W., Garren J. M., Calderwood S. B., John M. 2005; Identification of a protein subset of the anthrax spore immunome in humans immunized with the anthrax vaccine adsorbed preparation. Infect Immun 73:5685–5696 [CrossRef][PubMed]
    [Google Scholar]
  31. Little S. F., Ivins B. E., Fellows P. F., Pitt M. L., Norris S. L., Andrews G. P. 2004; Defining a serological correlate of protection in rabbits for a recombinant anthrax vaccine. Vaccine 22:422–430 [CrossRef][PubMed]
    [Google Scholar]
  32. Lyons C. R., Lovchik J., Hutt J., Lipscomb M. F., Wang E., Heninger S., Berliba L., Garrison K. 2004; Murine model of pulmonary anthrax: kinetics of dissemination, histopathology, and mouse strain susceptibility. Infect Immun 72:4801–4809 [CrossRef][PubMed]
    [Google Scholar]
  33. Mikesell P., Ivins B. E., Ristroph J. D., Dreier T. M. 1983; Evidence for plasmid-mediated toxin production in Bacillus anthracis . Infect Immun 39:371–376[PubMed]
    [Google Scholar]
  34. Mock M., Fouet A. 2001; Anthrax. Annu Rev Microbiol 55:647–671 [CrossRef][PubMed]
    [Google Scholar]
  35. Moody K. L., Driks A., Rother G. L., Cote C. K., Brueggemann E. E., Hines H. B., Friedlander A. M., Bozue J. 2010; Processing, assembly and localization of a Bacillus anthracis spore protein. Microbiology 156:174–183 [CrossRef][PubMed]
    [Google Scholar]
  36. Oliva C. R., Swiecki M. K., Griguer C. E., Lisanby M. W., Bullard D. C., Turnbough C. L. Jr, Kearney J. F. 2008; The integrin Mac-1 (CR3) mediates internalization and directs Bacillus anthracis spores into professional phagocytes. Proc Natl Acad Sci U S A 105:1261–1266 [CrossRef][PubMed]
    [Google Scholar]
  37. Pickering A. K., Osorio M., Lee G. M., Grippe V. K., Bray M., Merkel T. J. 2004; Cytokine response to infection with Bacillus anthracis spores. Infect Immun 72:6382–6389 [CrossRef][PubMed]
    [Google Scholar]
  38. Pitt M. L. M., Little S., Ivins B. E., Fellows P., Boles J., Barth J., Hewetson J., Friedlander A. M. 1999; In vitro correlate of immunity in an animal model of inhalational anthrax. J Appl Microbiol 87:304 [CrossRef][PubMed]
    [Google Scholar]
  39. Popov S. G., Popova T. G., Grene E., Klotz F., Cardwell J., Bradburne C., Jama Y., Maland M., Wells J. other authors 2004; Systemic cytokine response in murine anthrax. Cell Microbiol 6:225–233 [CrossRef][PubMed]
    [Google Scholar]
  40. Powell A. G., Crozier J. E., Hodgson H., Galloway D. J. 2011; A case of septicaemic anthrax in an intravenous drug user. BMC Infect Dis 11:21 [CrossRef][PubMed]
    [Google Scholar]
  41. Redmond C., Baillie L. W., Hibbs S., Moir A. J., Moir A. 2004; Identification of proteins in the exosporium of Bacillus anthracis . Microbiology 150:355–363 [CrossRef][PubMed]
    [Google Scholar]
  42. Ringertz S. H., Høiby E. A., Jensenius M., Maehlen J., Caugant D. A., Myklebust A., Fossum K. 2000; Injectional anthrax in a heroin skin-popper. Lancet 356:1574–1575 [CrossRef][PubMed]
    [Google Scholar]
  43. 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]
  44. Severson K. M., Mallozzi M., Bozue J., Welkos S. L., Cote C. K., Knight K. L., Driks A. 2009; Roles of the Bacillus anthracis spore protein ExsK in exosporium maturation and germination. J Bacteriol 191:7587–7596 [CrossRef]
    [Google Scholar]
  45. Shivachandra S. B., Li Q., Peachman K. K., Matyas G. R., Leppla S. H., Alving C. R., Rao M., Rao V. B. 2007; Multicomponent anthrax toxin display and delivery using bacteriophage T4. Vaccine 25:1225–1235 [CrossRef][PubMed]
    [Google Scholar]
  46. Shlyakhov E. N., Rubinstein E. 1994; Human live anthrax vaccine in the former USSR. Vaccine 12:727–730 [CrossRef][PubMed]
    [Google Scholar]
  47. Steichen C., Chen P., Kearney J. F., Turnbough C. L. Jr 2003; Identification of the immunodominant protein and other proteins of the Bacillus anthracis exosporium. J Bacteriol 185:1903–1910 [CrossRef][PubMed]
    [Google Scholar]
  48. Steichen C. T., Kearney J. F., Turnbough C. L. Jr 2005; Characterization of the exosporium basal layer protein BxpB of Bacillus anthracis . J Bacteriol 187:5868–5876 [CrossRef][PubMed]
    [Google Scholar]
  49. Sylvestre P., Couture-Tosi E., Mock M. 2002; A collagen-like surface glycoprotein is a structural component of the Bacillus anthracis exosporium. Mol Microbiol 45:169–178 [CrossRef][PubMed]
    [Google Scholar]
  50. Sylvestre P., Couture-Tosi E., Mock M. 2003; Polymorphism in the collagen-like region of the Bacillus anthracis BclA protein leads to variation in exosporium filament length. J Bacteriol 185:1555–1563 [CrossRef][PubMed]
    [Google Scholar]
  51. Sylvestre P., Couture-Tosi E., Mock M. 2005; Contribution of ExsFA and ExsFB proteins to the localization of BclA on the spore surface and to the stability of the Bacillus anthracis exosporium. J Bacteriol 187:5122–5128 [CrossRef][PubMed]
    [Google Scholar]
  52. Thompson B. M., Hsieh H.-Y., Spreng K. A., Stewart G. C. 2011; The co-dependence of BxpB/ExsFA and BclA for proper incorporation into the exosporium of Bacillus anthracis . Mol Microbiol 79:799–813 [CrossRef][PubMed]
    [Google Scholar]
  53. Todd S. J., Moir A. J., Johnson M. J., Moir A. 2003; Genes of Bacillus cereus and Bacillus anthracis encoding proteins of the exosporium. J Bacteriol 185:3373–3378 [CrossRef][PubMed]
    [Google Scholar]
  54. Turnbull P. C. 1991; Anthrax vaccines: past, present and future. Vaccine 9:533–539 [CrossRef][PubMed]
    [Google Scholar]
  55. Turnbull P. 2008 Anthrax in Humans and Animals, 4th edn. Geneva: WHO Press;
    [Google Scholar]
  56. Vergis J. M., Cote C. K., Bozue J., Alem F., Ventura C. L., Welkos S. L., O'Brien A. D. 2011 Protection from challenge with B. anthracis Sterne or Ames after immunization with plasmid-cured B. cereus G9241 spores. In: International Bacillus-ACT Meeting, p. 74, Bruges, Belgium
  57. Wasserman G. M., Grabenstein J. D., Pittman P. R., Rubertone M. V., Gibbs P. P., Wang L. Z., Golder L. G. 2003; Analysis of adverse events after anthrax immunization in US Army medical personnel. J Occup Environ Med 45:222–233 [CrossRef][PubMed]
    [Google Scholar]
  58. Welkos S. L., Friedlander A. M. 1988; Comparative safety and efficacy against Bacillus anthracis of protective antigen and live vaccines in mice. Microb Pathog 5:127–139 [CrossRef][PubMed]
    [Google Scholar]
  59. Welkos S. L., Keener T. J., Gibbs P. H. 1986; Differences in susceptibility of inbred mice to Bacillus anthracis . Infect Immun 51:795–800[PubMed]
    [Google Scholar]
  60. Welkos S. L., Becker D., Friedlander A., Trotter R. 1989; Pathogenesis and host resistance to Bacillus anthracis: a mouse model. Salisbury Med Bull 68:49–52
    [Google Scholar]
  61. Welkos S. L., Vietri N. J., Gibbs P. H. 1993; Non-toxigenic derivatives of the Ames strain of Bacillus anthracis are fully virulent for mice: role of plasmid pX02 and chromosome in strain-dependent virulence. Microb Pathog 14:381–388 [CrossRef][PubMed]
    [Google Scholar]
  62. Welkos S. L., Cote C. K., Rea K. M., Gibbs P. H. 2004; A microtiter fluorometric assay to detect the germination of Bacillus anthracis spores and the germination inhibitory effects of antibodies. J Microbiol Methods 56:253–265 [CrossRef][PubMed]
    [Google Scholar]
  63. Williamson E. D., Hodgson I., Walker N. J., Topping A. W., Duchars M. G., Mott J. M., Estep J., Lebutt C., Flick-Smith H. C. other authors 2005; Immunogenicity of recombinant protective antigen and efficacy against aerosol challenge with anthrax. Infect Immun 73:5978–5987 [CrossRef][PubMed]
    [Google Scholar]
  64. Young J. A., Collier R. J. 2007; Anthrax toxin: receptor binding, internalization, pore formation, and translocation. Annu Rev Biochem 76:243–265 [CrossRef][PubMed]
    [Google Scholar]
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