A dually active anthrax vaccine that confers protection against both bacilli and toxins.
Gi-eun Rhie,Michael H. Roehrl,Michael Mourez,R. John Collier,John J. Mekalanos,Julia Y. Wang +5 more
TLDR
DAAV combines both antibacterial and antitoxic components in a single vaccine against anthrax, introducing a vaccine design that may be widely applicable against infectious diseases and provides additional tools in medicine and biodefense.Abstract:
Systemic anthrax is caused by unimpeded bacillar replication and toxin secretion. We developed a dually active anthrax vaccine (DAAV) that confers simultaneous protection against both bacilli and toxins. DAAV was constructed by conjugating capsular poly-γ-d-glutamic acid (PGA) to protective antigen (PA), converting the weakly immunogenic PGA to a potent immunogen, and synergistically enhancing the humoral response to PA. PGA-specific antibodies bound to encapsulated bacilli and promoted the killing of bacilli by complement. PA-specific antibodies neutralized toxin activity and protected immunized mice against lethal challenge with anthrax toxin. Thus, DAAV combines both antibacterial and antitoxic components in a single vaccine against anthrax. DAAV introduces a vaccine design that may be widely applicable against infectious diseases and provides additional tools in medicine and biodefense.read more
Citations
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Journal ArticleDOI
Binary Bacterial Toxins: Biochemistry, Biology, and Applications of Common Clostridium and Bacillus Proteins
TL;DR: This review comprehensively surveys the literature and discusses the similarities and distinct differences between each Clostridium and Bacillus binary toxin in terms of their biochemistry, biology, genetics, structure, and applications in science and medicine.
Journal ArticleDOI
Key role of poly-γ-dl-glutamic acid in immune evasion and virulence of Staphylococcus epidermidis
Stanislava Kocianova,Cuong Vuong,Yufeng Yao,Jovanka M. Voyich,Elizabeth R. Fischer,Frank R. DeLeo,Michael Otto +6 more
TL;DR: It is demonstrated that S. epidermidis secretes poly-gamma-DL-glutamic acid (PGA) to facilitate growth and survival in the human host and indicates that PGA represents an excellent target for therapeutic maneuvers aimed at treating disease caused by S. EpidermidIS and related staphylococci.
Book ChapterDOI
Biodegradable Nanoparticles as Vaccine Adjuvants and Delivery Systems: Regulation of Immune Responses by Nanoparticle-Based Vaccine
TL;DR: Nanoparticles prepared from biodegradable and biocompatible polymers such as poly(lactide-co-glycolide) (PLGA), poly(amino acid)s, and polysaccharides have been shown to be effective.
Book ChapterDOI
Rho-modifying C3-like ADP-ribosyltransferases.
TL;DR: The present review indicates that the functional consequences of C3-induced ADP-ribosylation are more complex than previously suggested.
Journal ArticleDOI
Capsule synthesis by Bacillus anthracis is required for dissemination in murine inhalation anthrax
TL;DR: It is shown that a strain carrying both virulence plasmids but deleted specifically for capBCAD is highly attenuated in a mouse model for inhalation anthrax, indicating that acpA and acpB are not true functional homologs and that acPB may play a larger role in virulence than originally suspected.
References
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Thomas V. Inglesby,Tara O'Toole,Donald A. Henderson,John G. Bartlett,Michael S. Ascher,Edward M. Eitzen,Arthur M. Friedlander,Julie L. Gerberding,Jerome Hauer,James M. Hughes,Joseph E. McDade,Michael T. Osterholm,Gerald W. Parker,Trish M. Perl,Philip K. Russell,Kevin Tonat +15 more
TL;DR: This revised consensus statement presents new information based on the analysis of the anthrax attacks of 2001, including developments in the investigation of the Anthrax Attacks of 2001; important symptoms, signs, and laboratory studies; new diagnostic clues that may help future recognition of this disease; updated antibiotic therapeutic considerations; and judgments about environmental surveillance and decontamination.
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Expression of two csg operons is required for production of fibronectin‐ and Congo red‐binding curli polymers in Escherichia coli K‐12
TL;DR: Two divergently transcribed operons in Escherichia coli required for the expression of fibronectin‐ and Congo red‐binding curli polymers were identified and characterized by transposon mutagenesis, sequencing and transcriptional analyses, as well as for their ability to produce the curli subunit protein.
Journal ArticleDOI
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TL;DR: It is found that B. anthracis lethal factor selectively induces apoptosis of activated macrophages by cleaving the amino-terminal extension of mitogen-activated protein kinase (MAPK) kinases (MKKs) that activate p38 MAPKs.
Journal ArticleDOI
Molecular characterization and protein analysis of the cap region, which is essential for encapsulation in Bacillus anthracis.
TL;DR: It was found that the capsule of B. anthracis conferred strong resistance to phagocytosis upon the bacterial host, and these three cistrons appeared to be membrane-associated enzymes mediating the polymerization of D-glutamic acid via the membrane.
Journal ArticleDOI
Designing a polyvalent inhibitor of anthrax toxin
Michael Mourez,Ravi S. Kane,Jeremy Mogridge,Steve Metallo,Pascal Deschatelets,Bret R. Sellman,George M. Whitesides,R. John Collier +7 more
TL;DR: This work isolated a peptide from a phage display library that binds weakly to the heptameric cell-binding subunit of anthrax toxin and prevents the interaction between cell- binding and enzymatic moieties.