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

Cote, Christopher K.; Rossi, Cynthia A.; Kang, Angray S.; Morrow, Phillip R.; Lee, J.S.; Welkos, Susan L.

doi:10.1016/j.micpath.2005.02.001

Cited by 109 publications

(78 citation statements)

References 40 publications

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“…Cote et al (24) reported that anti-PA Abs can increase the phagocytosis and destruction of spores. This observation and the data reported in this study, when taken together, may explain why mice immunized with both PA and FIS are more protected than those immunized with PA alone.…”

Section: Discussionmentioning

confidence: 99%

Cutting Edge: IFN-γ-Producing CD4 T Lymphocytes Mediate Spore-Induced Immunity to Capsulated Bacillus anthracis

Glomski

Corre

Mock

et al. 2007

The Journal of Immunology

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Virulent strains of Bacillus anthracis produce immunomodulating toxins and an antiphagocytic capsule. The toxin component-protective Ag is a key target of the antianthrax immune response that induces production of toxin-neutralizing Abs. Coimmunization with spores enhances the antitoxin vaccine, and inactivated spores alone confer measurable protection. We aimed to identify the mechanisms of protection induced in inactivated-spore immunized mice that function independently of the toxin/antitoxin vaccine system. This goal was addressed with humoral and CD4 T lymphocyte transfer, in vivo depletion of CD4 T lymphocytes and IFN-γ, and Ab-deficient (μMT−/−) or IFN-γ-insensitive (IFN-γR−/−) mice. We found that humoral immunity did not protect from nontoxinogenic capsulated bacteria, whereas a cellular immune response by IFN-γ-producing CD4 T lymphocytes protected mice. These results are the first evidence of protective cellular immunity against capsulated B. anthracis and suggest that future antianthrax vaccines should strive to augment cellular adaptive immunity.

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Section: Discussionmentioning

confidence: 99%

Cutting Edge: IFN-γ-Producing CD4 T Lymphocytes Mediate Spore-Induced Immunity to Capsulated Bacillus anthracis

Glomski

Corre

Mock

et al. 2007

The Journal of Immunology

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“…Retention of the pXO1 and pXO2 plasmids was assayed by PCR using primers specific for the pagA (15) and capC genes, respectively. Capsule production was verified in all strains by growth on Trypticase soy agar (TSA) plates containing bicarbonate.…”

Section: Methodsmentioning

confidence: 99%

“…At various time points after inoculation, an aliquot was removed from each culture; the aliquot was centrifuged to pellet the cells; and the supernatant was removed. Western blotting of the supernatants from each sample was then performed using rabbit anti-PA antibodies (15).…”

Section: Methodsmentioning

confidence: 99%

Role of Purine Biosynthesis in Bacillus anthracis Pathogenesis and Virulence

et al. 2011

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Bacillus anthracis, the etiological agent of anthrax, is a spore-forming, Gram-positive bacterium and a category A biothreat agent. Screening of a library of transposon-mutagenized B. anthracis spores identified a mutant displaying an altered phenotype that harbored a mutated gene encoding the purine biosynthetic enzyme PurH. PurH is a bifunctional protein that catalyzes the final steps in the biosynthesis of the purine IMP. We constructed and characterized defined purH mutants of the virulent B. anthracis Ames strain. The virulence of the purH mutants was assessed in guinea pigs, mice, and rabbits. The spores of the purH mutants were as virulent as wild-type spores in mouse intranasal and rabbit subcutaneous infection models but were partially attenuated in a mouse intraperitoneal model. In contrast, the purH mutant spores were highly attenuated in guinea pigs regardless of the administration route. The reduced virulence in guinea pigs was not due solely to a germination defect, since both bacilli and toxins were detected in vivo, suggesting that the significant attenuation was associated with a growth defect in vivo. We hypothesize that an intact purine biosynthetic pathway is required for the virulence of B. anthracis in guinea pigs.

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“…The ability of PA to elicit antibody responses and to protect animals from challenge has been demonstrated in a number of studies and that antibody responses in rabbits have been shown to correlate with protection [5][6][7][8][9][10]. In addition, anti-PA antibodies have been shown to function to prevent the effects of anthrax toxin [11,12], and also appear to inhibit spore germination and enhance the phagocytic and sporicidal activity of macrophages [12,13]. In anthrax vaccination studies using the VEE replicon, our group previously showed complete protection of A/J and CBA/J mice inoculated subcutaneously with VRP expressing the mature 83-kDa PA gene (MAT-PA) against a B. anthracis (Sterne strain) challenge [14].…”

Section: Introductionmentioning

confidence: 99%

Multiagent vaccines vectored by Venezuelan equine encephalitis virus replicon elicits immune responses to Marburg virus and protection against anthrax and botulinum neurotoxin in mice

Lee

Groebner

Hadjipanayis

et al. 2006

Vaccine

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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

Cited by 109 publications

References 40 publications

Cutting Edge: IFN-γ-Producing CD4 T Lymphocytes Mediate Spore-Induced Immunity to Capsulated Bacillus anthracis

Cutting Edge: IFN-γ-Producing CD4 T Lymphocytes Mediate Spore-Induced Immunity to Capsulated Bacillus anthracis

Role of Purine Biosynthesis in Bacillus anthracis Pathogenesis and Virulence

Multiagent vaccines vectored by Venezuelan equine encephalitis virus replicon elicits immune responses to Marburg virus and protection against anthrax and botulinum neurotoxin in mice

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