Topic
Bacillus anthracis
About: Bacillus anthracis is a research topic. Over the lifetime, 3994 publications have been published within this topic receiving 128122 citations.
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TL;DR: Bordetella pertussis and Bacillus anthracis each produce a virulence-associated, calmodulin-dependent adenylate cyclase toxin, which generates increased levels of cyclic AMP in eukaryotic cells.
57 citations
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TL;DR: This review summarizes the work of numerous laboratories in the search for alternative vaccines against anthrax that are well tolerated, provide long-lasting immunity, and are efficacious.
Abstract: The current human anthrax vaccines licensed in the US and UK consist of aluminum hydroxide-adsorbed or alum-precipitated culture supernatant material from fermentor cultures of toxigenic noncapsulated strains of Bacillus anthracis. The threat of B. anthracis being used as a biowarfare agent has led to a wider usage of these vaccines, which has heightened concerns regarding the need for frequent boosters and the occasional local reactogenicity associated with vaccination. These concerns have provided the impetus for the development of better characterized vaccines. This review summarizes the work of numerous laboratories in the search for alternative vaccines against anthrax that are well tolerated, provide long-lasting immunity, and are efficacious.
57 citations
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57 citations
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TL;DR: In conclusion, anthrax toxin inhibits the priming that is normally induced in PMN by bacterial products and is necessary for the full expression of antimicrobial effects.
Abstract: We studied the pretreatment of human polymorphonuclear neutrophils (PMN) with purified preparations of the anthrax toxin components--protective antigen (PA), edema factor (EF), and lethal factor (LF)--and their effects on release of superoxide anion (O-2) after stimulation with the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP). PMN isolated in the absence of lipopolysaccharide (LPS) (less than 0.1 ng/ml) released only small amounts of O-2 after FMLP stimulation; pretreatment with anthrax toxin had little effect. The release of O-2 was increased fivefold by prior treatment with 3 ng/ml LPS for 1 h at 37 degrees C, an effect referred to as priming. PMN were primed to an equivalent extent by treatment with 100 ng/ml N-acetyl-muramyl-L-alanyl-D-isoglutamine (muramyl dipeptide [MDP]). Pretreatment of PMN with anthrax toxin components PA plus EF or PA plus LF inhibited priming by LPS or MDP, as shown by the reduction in the release of O-2 up to 90% relative to controls not treated with toxin; single toxin components were inactive. The inhibition was markedly reduced when priming with LPS or MDP was carried out before exposure to toxin. O-2 release after stimulation by phorbol myristate acetate was not increased by priming, and pretreatment with toxin did not inhibit O-2 release after this stimulus. Evidently, anthrax toxin inhibits the priming that is normally induced in PMN by bacterial products and is necessary for the full expression of antimicrobial effects.
57 citations
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TL;DR: This pI:C-adjuvanted rPA vaccine has the potential to be developed into an efficacious nasal anthrax vaccine.
Abstract: The current anthrax vaccine adsorbed (AVA) was originally licensed for the prevention of cutaneous anthrax infection. It has many drawbacks, including the requirement for multiple injections and subsequent annual boosters. Thus, an easily administrable and efficacious anthrax vaccine is needed to prevent the most lethal form of anthrax infection, inhalation anthrax. We propose to develop a nasal anthrax vaccine using anthrax protective antigen (PA) protein as the antigen and synthetic double-stranded RNA in the form of polyriboinosinic–polyribocytidylic acid (pI:C) as an adjuvant. Mice were nasally immunized with recombinant PA admixed with pI:C. The resulting PA-specific antibody responses and the lethal toxin neutralization activity were measured. Moreover, the effect of pI:C on dendritic cells (DCs) was evaluated both in vivo and in vitro. Mice nasally immunized with rPA adjuvanted with pI:C developed strong systemic and mucosal anti-PA responses with lethal toxin neutralization activity. These immune responses compared favorably to that induced by nasal immunization with rPA adjuvanted with cholera toxin. Poly(I:C) enhanced the proportion of DCs in local draining lymph nodes and stimulated DC maturation. This pI:C-adjuvanted rPA vaccine has the potential to be developed into an efficacious nasal anthrax vaccine.
57 citations