The terrorist attacks of 2001 involving anthrax underscore the imperative that safe and effective medical countermeasures should be readily available. Vaccination appears to be the most effective form of mass protection against a biological attack, but the current vaccines have drawbacks that justify the enormous amount of effort currently being put into developing more effective vaccines and other treatment modalities. After providing a comprehensive overview of the organism Bacillus anthracis as a biological weapon and its pathogenicity, this review briefly summarizes the current knowledge vital to the management of anthrax disease. This knowledge has been acquired since 2001 as a result of the progress on anthrax research and focuses on the possible development of improved human anti-infective strategies targeting B. anthracis spore components, as well as strategies based on host–pathogen interactions.

Potential biological targets of Bacillus anthracis in anti-infective approaches against the threat of bioterrorism.

Chimeric hepatitis B virus core particles carrying an epitope of anthrax protective antigen induce protective immunity against Bacillus anthracis

Single-step purification of recombinant anthrax lethal factor from periplasm of Escherichia coli.

Protection against anthrax and plague by a combined vaccine in mice and rabbits.

Secretory expression and efficient purification of recombinant anthrax toxin lethal factor with full biological activity in E. coli.

The gene encoding anthrax lehtal factor (LF) was cloned into a secretory expression plasmid and then expressed in periplasmic space of E. coli. The recombinant LF (rLF) expressed was about 4% of the total proteins in E. coli. About 3 mg electrophoresis purity rLF could be obtained after the purification of 1 liter culure using ion exchange chromatography and gel filtration. The result of sequencing assay showed that the N-terminal amino acid sequence of rLF was identical to the N-terminal sequence of natural LF. In vitro toxicity analysis also shows that rLF has an excellent biological activity. The successful expression of rLF has placed a solid foundation for the research on toxicity mechanism of LF, developing new anthrax vaccines, and screening for inhibitors against anthrax toxin.

Expression and characterization of the recombination anthrax lethal factor

Anthrax toxin from Bacillus anthracis is a three-component toxin consisting of lethal factor (LF), edema factor (EF), and protective antigen (PA) PA binds to target cells and transports LF or EF into the cell cytosol where they carry out their enzymatic functions PA can induce protective immunity to the infection of the bacterium and is the major component in the only anthrax vaccine approved by FDA of USA Mouse hybridoma clones specifically secreting anti-PA monoclonal antibodies (MAbs) were generated by cell fusion technique and their ability to neutralize anthrax lethal toxin activities was screened in vitro on a toxin-sensitive cell line Nine toxin-neutralizing MAbs obtained were then characterized for the domains of PA they recognize, and the epitope regions they bind were analyzed by competitive binding ELISA It was found that these MAbs bind four potential neutralizing epitope regions in three different domains of PA Four MAbs bind to two non-overlapping epitope regions in domain 4 of PA and may prevent the binding of PA to its cell receptor Four MAbs bind to domain 2, a domain involved in membrane insertion One MAb binds to domain 3, a region involved in the oligomerization of PA The results provided supporting evidence that PA has several neutralizing epitopes, and offered potential immunotherapeutic agents for the treatment of anthrax

Qiang Guo

Papers

Expression and characterization of the recombination anthrax lethal factor

[Toxin-neutralizing monoclonal antibodies to the different domains of anthrax protective antigen].