The development of new vaccines against Bacillus anthracis

Baillie, Les

doi:10.1046/j.1365-2672.2001.01498.x

Cited by 59 publications

(55 citation statements)

References 41 publications

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“…Indeed, we found that NOD2 can associate with NALP1 to form a complex that activates caspase-1 in response to MDP. Importantly, NOD2 is a critical mediator of IL-1␤ secretion during Bacillus anthracis infection and thus may be an important contributor to the severe inflammation associated with Anthrax (15).…”

Section: Nod2 a Nod-like Receptor (Nlr)mentioning

confidence: 99%

A NOD2–NALP1 complex mediates caspase-1-dependent IL-1β secretion in response to Bacillus anthracis infection and muramyl dipeptide

Hsu

Ali²,

McGillivray³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

339

306

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NOD2, a NOD-like receptor (NLR), is an intracellular sensor of bacterial muramyl dipeptide (MDP) that was suggested to promote secretion of the proinflammatory cytokine IL-1␤. Yet, the molecular mechanism by which NOD2 can stimulate IL-1␤ secretion, and its biological significance were heretofore unknown. We found that NOD2 through its N-terminal caspase recruitment domain directly binds and activates caspase-1 to trigger IL-1␤ processing and secretion in MDP-stimulated macrophages, whereas the C-terminal leucine-rich repeats of NOD2 prevent caspase-1 activation in nonstimulated cells. MDP challenge induces the association of NOD2 with another NLR protein, NALP1, and gel filtration analysis revealed the formation of a complex consisting of NOD2, NALP1, and caspase-1. Importantly, Bacillus anthracis infection induces IL-1␤ secretion in a manner that depended on caspase-1 and NOD2. In vitro, Anthrax lethal toxin strongly potentiated IL-1␤ secretion, and that response was NOD2 and caspase-1-dependent. Thus, NOD2 plays a key role in the B. anthracis-induced inflammatory response by being a critical mediator of IL-1␤ secretion.inflammasome ͉ lethal toxin ͉ LPS

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Section: Nod2 a Nod-like Receptor (Nlr)mentioning

confidence: 99%

A NOD2–NALP1 complex mediates caspase-1-dependent IL-1β secretion in response to Bacillus anthracis infection and muramyl dipeptide

Hsu

Ali²,

McGillivray³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

339

306

View full text Add to dashboard Cite

show abstract

“…In the United Kingdom, the human-use anthrax vaccine, alum-precipitated antigen (APA), is prepared by adsorbing filtered culture supernatant fluids of the 34F 2 Sterne strain of B. anthracis to potassium aluminum sulfate (alum) [3]. The current potency assays for both AVA Biothrax and APA are based upon protection of guinea pigs vaccinated against a parenteral B. anthracis spore challenge.…”

Section: Bacillus Anthracis To Aluminum Hydroxide Gel (Alhydrogel)mentioning

confidence: 99%

Development of an in vitro-based potency assay for anthrax vaccine

Little

Webster

Ivins

et al. 2004

Vaccine

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“…The availability of a crystal structure for PA (7) has contributed to a clearer picture of the location of binding sites for the host cell PA receptor (8) and the other toxin subunits (9,10) in relation to the four domains of the PA molecule. In addition to a role in virulence, PA is the main target of protective immunity to anthrax and is thought to induce T-cell-dependent antibodies that protect the host by preventing toxin assembly and internalization (11)(12)(13)(14)(15). Consequently, PA is the major antigenic component of the current anthrax vaccine, and subunit vaccines based on truncated recombinant PA molecules are under development (16).…”

mentioning

confidence: 99%

Differential Processing of CD4 T-cell Epitopes from the Protective Antigen of Bacillus anthracis

Musson

Walker

Flick-Smith

et al. 2003

Journal of Biological Chemistry

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We have mapped CD4؉ T-cell epitopes located in three domains of the recombinant protective antigen of Bacillus anthracis. Mouse T-cell hybridomas specific for these epitopes were generated to study the mechanisms of proteolytic processing of recombinant protective antigen for antigen presentation by bone marrow-derived macrophages. Overall, epitopes differed considerably in their processing requirements. In particular, the kinetics of presentation, ranging from 15 (fast) to 120 min (slow), suggested sequential liberation of epitopes during proteolytic processing of the intact PA molecule. Pretreatment of macrophages with ammonium chloride or inhibitors of the major enzyme families showed that T-cell responses to an epitope presented with fast kinetics were unaffected by raising endosomal pH or inhibiting cysteine or aspartic proteinases, suggesting presentation independent of lysosomal processing. In contrast, responses to epitopes presented with slower kinetics were dependent on low pH and the activity of cysteine or aspartic proteinases indicating a requirement for lysosomal processing. In addition, responses to all epitopes, whether their presentation was dependent on low pH or not, were prevented by treatment of macrophages with broad spectrum serine proteinase inhibitors. Thus, our data are consistent with a model of sequential antigen processing within the endosomal system, beginning with a pre-processing step mediated by serine or metalloproteinases prior to further processing by lysosomal enzymes. Rapidly presented epitopes seemed to require only limited proteolysis at earlier stages of endocytosis, whereas the majority of epitopes required more extensive processing by neutral proteinases followed by lysosomal enzymes.

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The development of new vaccines against Bacillus anthracis

Cited by 59 publications

References 41 publications

A NOD2–NALP1 complex mediates caspase-1-dependent IL-1β secretion in response to Bacillus anthracis infection and muramyl dipeptide

A NOD2–NALP1 complex mediates caspase-1-dependent IL-1β secretion in response to Bacillus anthracis infection and muramyl dipeptide

Development of an in vitro-based potency assay for anthrax vaccine

Differential Processing of CD4 T-cell Epitopes from the Protective Antigen of Bacillus anthracis

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