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Anthrax
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1. Protective antigen as a correlative marker for anthrax in animal models.
Match Strength: 8.649

The most aggressive form of anthrax results from inhalation of airborne spores of Bacillus anthracis and usually progresses unnoticed in the early stages because of unspecific symptoms. The only reliable marker of anthrax is development of bacteremia, which increases with disease progress. Rapid diagnosis of anthrax is imperative for efficient treatment and cure. Herein we demonstrate that the presence and level of a bacterial antigen, the protective antigen (PA), a component of B. anthracis toxins, in host sera can serve as a reliable marker of infection. This was tested in two animal models ... Read More »
» Published in Infect Immun. 2006 Oct;74(10):5871-6.

2. Prophylaxis and therapy of inhalational anthrax by a novel monoclonal antibody to protective antigen that mimics vaccine-induced immunity.
Match Strength: 8.184

The neutralizing antibody response to the protective antigen (PA) component of anthrax toxin elicited by approved anthrax vaccines is an accepted correlate for vaccine-mediated protection against anthrax. We reasoned that a human anti-PA monoclonal antibody (MAb) selected on the basis of superior toxin neutralization activity might provide potent protection against anthrax. The fully human MAb (also referred to as MDX-1303 or Valortim) was chosen from a large panel of anti-PA human MAbs generated using transgenic mice immunized with recombinant PA solely on the basis of in vitro anthrax toxin ... Read More »
» Published in Infect Immun. 2006 Oct;74(10):5840-7.

3. Recombinant protective antigen 102 (rPA102): profile of a second-generation anthrax vaccine.
Match Strength: 8.142

Recent terrorist attacks involving the use of Bacillus anthracis spores have stimulated interest in the development of new vaccines for anthrax prevention. Studies of the pathogenesis of anthrax and of the immune responses following infection and immunization underscore the pivotal role that antibodies to the protective antigen play in protection. The most promising vaccine candidates contain purified recombinant protective antigen. Clinical trials of one of these, recombinant protective antigen (rPA)102, are underway. Initial results suggest that rPA102 is well tolerated and immunogenic. ... Read More »
» Published in Expert Rev Vaccines. 2006 Aug;5(4):417-30.

4. Search for cyclodextrin-based inhibitors of anthrax toxins: synthesis, structural features, and relative activities.
Match Strength: 7.163

Recently, using structure-inspired drug design, we demonstrated that aminoalkyl derivatives of beta-cyclodextrin inhibited anthrax lethal toxin action by blocking the transmembrane pore formed by the protective antigen (PA) subunit of the toxin. In the present study, we evaluate a series of new beta-cyclodextrin derivatives with the goal of identifying potent inhibitors of anthrax toxins. Newly synthesized hepta-6-thioaminoalkyl and hepta-6-thioguanidinoalkyl derivatives of beta-cyclodextrin with alkyl spacers of various lengths were tested for the ability to inhibit cytotoxicity of lethal ... Read More »
» Published in Antimicrob Agents Chemother. 2006 Nov;50(11):3740-53. Epub 2006 Sep 18.

5. Immunization against anthrax using Bacillus subtilis spores expressing the anthrax protective antigen.
Match Strength: 6.436

Protective immunity to anthrax can be achieved by antibodies raised against the secreted protective antigen (PA) and this forms the basis of the current acellular vaccines for human use. Bacillus subtilis spores have previously been used for delivery of heterologous antigens by the oral and nasal routes and their intrinsic heat-stability make them attractive vaccine vehicles. In this study we have expressed PA, or segments of PA, in B. subtilis using two strategies. First, display on the spore coat, and second, in the germinated spore (or vegetative cell). Using parenteral delivery we show ... Read More »
» Published in Vaccine. 2007 Jan 4;25(2):346-55. Epub 2006 Aug 4.

6. Detection and phylogenic analysis of one anthrax virulence plasmid pXO1 conservative open reading frame ubiquitous presented within Bacillus cereus group strains.
Match Strength: 5.329

The presence of one of the anthrax virulence plasmid pXO1 conserved fragments was analyzed in 24 Bacillus cereus and B. thuringiensis strains, including 6 B. thuringiensis subspecies, by polymerase chain reactions. Twelve out of 24 strains showed PCR-positive for an ORF101 homologous sequence. Two pXO1-ORF101-like fragments from a B. cereus B-4ac and a commercial B. thuringiensis kurstaki HD1 were cloned, sequenced and expressed in Escherichia coli. Toxicity assays revealed that the product encoded by the pXO1-ORF101-like fragment had no impact on either Vero cells or Chinese Hamster Ovary ... Read More »
» Published in Biochem Biophys Res Commun. 2006 Nov 3;349(4):1214-9. Epub 2006 Aug 31.

7. Increased potency of BioThrax anthrax vaccine with the addition of the C-class CpG oligonucleotide adjuvant CPG 10109.
Match Strength: 5.037

The inclusion of an adjuvant, in addition to the existing aluminum hydroxide, in the formulation of the licensed anthrax vaccine BioThrax may have the potential to positively modify immune responses. Some potential desirable outcomes from the inclusion of an additional adjuvant include increased immune response kinetics, increased response rates, more prolonged antibody decay rates, and the ability to use less antigen per dose or fewer doses to achieve immunity. One promising group of adjuvants that is being investigated with a variety of vaccines and which has been shown to cause many of ... Read More »
» Published in Vaccine. 2007 Jan 5;25(3):526-34. Epub 2006 Aug 17.

8. Significant passive protective effect against anthrax by antibody to Bacillus anthracis inactivated spores that lack two virulence plasmids.
Match Strength: 4.075

The protective-antigen (PA)-based cell-free vaccine is the only vaccine licensed for use against Bacillus anthracis infection in humans. Although the PA shows strong immunogenicity, the capsule or spore-associated somatic antigens may be important as additional vaccine targets for full protection against anthrax. In this study, the protective effect of spore-associated antigens against B. anthracis infection was determined. Rabbits were immunized with formalin-fixed spores of a non-toxigenic unencapsulated B. anthracis strain that lacked the two virulence plasmids pXO1 and pXO2, and the ... Read More »
» Published in Microbiology. 2006 Oct;152(Pt 10):3103-10.

9. Inactivation of Bacillus anthracis spores in murine primary macrophages.
Match Strength: 2.751

The current model for pathogenesis of inhalation anthrax indicates that the uptake and fate of Bacillus anthracis spores in alveolar macrophages are critical to the infection process. We have employed primary macrophages, which are more efficient for spore uptake than the macrophage-like cell line RAW264.7, to investigate spore uptake and survival. We found that at a multiplicity of infection (moi) of 5, greater than 80% of the spores of the Sterne strain containing only the pXO1 plasmid were internalized within 1 h. Within 4 h post infection, viability of internalized Sterne spores decreased ... Read More »
» Published in Cell Microbiol. 2006 Oct;8(10):1634-42.

10. Structure-activity relationships of Bacillus cereus and Bacillus anthracis dihydrofolate reductase: toward the identification of new potent drug leads.
Match Strength: 2.719

New and improved therapeutics are needed for Bacillus anthracis, the etiological agent of anthrax. To date, antimicrobial agents have not been developed against the well-validated target dihydrofolate reductase (DHFR). In order to address whether DHFR inhibitors could have potential use as clinical agents against Bacillus, 27 compounds were screened against this enzyme from Bacillus cereus, which is identical to the enzyme from B. anthracis at the active site. Several 2,4-diamino-5-deazapteridine compounds exhibit submicromolar 50% inhibitory concentrations (IC(50)s). Four of the inhibitors ... Read More »
» Published in Antimicrob Agents Chemother. 2006 Oct;50(10):3435-43.

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