The development of new vaccines against Bacillus anthracis

The disease anthrax is caused by a bacterium, Bacillus anthracis. Although primarily a disease of animals it can also infect man, sometimes with fatal consequences. Recent interest in the organism has centred on its ability to be employed as a biological weapon; the organism forms heat resistant spores which are easy to produce using commercially available technology and can infect humans via the aerosol route. At the time of the Gulf War it was reported that Iraq had produced and weaponized large quantities of anthrax spores (Zilinska 1997; www.anthrax.osd.mil/). As a consequence of this raised pro®le a considerable amount of effort has been focused on the development of new therapies that will meet the standards of the 21st century. Vaccination is the most cost-effective form of mass protection. While the ®rst anthrax animal vaccine was developed by Pasteur in 1881, human vaccines did not emerge until the middle of the 20th century. The vaccines currently available provide effective protection but suffer from problems of standardization, are relatively expensive to produce, require repeated dosing and have been associated with transient side-effects. This paper will give a brief overview of the organism, its pathogenicity and the efforts being made to develop new vaccines.

[1]  B. Ivins,et al.  Molecular pathogenesis of Bacillus anthracis infection. , 1999, Microbes and infection.

[2]  M. Shaw,et al.  Expression of the protective antigen of Bacillus anthracis by Lactobacillus casei: towards the development of an oral vaccine against anthrax. , 1999, Journal of applied microbiology.

[3]  S. Welkos,et al.  Cloning and expression of the Bacillus anthracis protective antigen gene in Bacillus subtilis , 1986, Infection and immunity.

[4]  P. Turnbull Current status of immunization against anthrax: old vaccines may be here to stay for a while. , 2000, Current opinion in infectious diseases.

[5]  B. Ivins,et al.  Comparative efficacy of experimental anthrax vaccine candidates against inhalation anthrax in rhesus macaques. , 1996, Vaccine.

[6]  Belton Fc,et al.  Studies on a protective antigen produced in vitro from Bacillus anthracis: medium and methods of production. , 1954 .

[7]  T. Read,et al.  Bacillus anthracis, a bug with attitude! , 2001, Current opinion in microbiology.

[8]  M. Doğanay,et al.  Antimicrobial susceptibility of Bacillus anthracis. , 1991, Scandinavian journal of infectious diseases.

[9]  M. Sterne Distribution and economic importance of anthrax. , 1967, Federation proceedings.

[10]  S. Leppla,et al.  Internalization and processing of Bacillus anthracis lethal toxin by toxin-sensitive and -resistant cells. , 1989, The Journal of biological chemistry.

[11]  R. Zilinskas,et al.  Iraq's biological weapons. The past as future? , 1997, JAMA.

[12]  L. Tran,et al.  Engineering a Bacillus subtilis expression-secretion system with a strain deficient in six extracellular proteases , 1991, Journal of bacteriology.

[13]  P. Hambleton,et al.  Anthrax: the disease in relation to vaccines. , 1984, Vaccine.

[14]  P. Turnbull,et al.  Anthrax vaccines: past, present and future. , 1991, Vaccine.

[15]  P. Turnbull Definitive identification of Bacillus anthracis—a review , 1999, Journal of applied microbiology.

[16]  L. Price,et al.  Multiple-Locus Variable-Number Tandem Repeat Analysis Reveals Genetic Relationships within Bacillus anthracis , 2000, Journal of bacteriology.

[17]  M. Shaw,et al.  Expression of the protective antigen of Bacillus anthracis by Lactobacillus casei: towards the development of an oral vaccine against anthrax , 1999 .

[18]  S. Leppla,et al.  Protection against anthrax toxin by vaccination with a DNA plasmid encoding anthrax protective antigen. , 1999, Vaccine.

[19]  L. Baillie,et al.  Presentation of protective antigen to the mouse immune system: immune sequelae , 1999, Journal of applied microbiology.

[20]  M. Johnson,et al.  Evaluation of Bacillus subtilis strain IS53 for the production of Bacillus anthracis protective antigen , 1994, Letters in applied microbiology.

[21]  Moir,et al.  The expression of the protective antigen of Bacillusanthracis in Bacillus subtilis , 1998, Journal of applied microbiology.

[22]  K D Paull,et al.  Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor. , 1998, Science.

[23]  S. Leppla,et al.  Cloning of the protective antigen gene of Bacillus anthracis , 1983, Cell.

[24]  Mcbride,et al.  Production and purification of recombinant protective antigen and protective efficacy against Bacillusanthracis , 1998, Letters in applied microbiology.

[25]  P. Hanna,et al.  Understanding Bacillus anthracis pathogenesis. , 1999, Trends in microbiology.

[26]  J. Ezzell,et al.  Postexposure prophylaxis against experimental inhalation anthrax. , 1993, The Journal of infectious diseases.

[27]  J. Dalrymple,et al.  Expression of the Bacillus anthracis protective antigen gene by baculovirus and vaccinia virus recombinants , 1990, Infection and immunity.

[28]  R. Liddington,et al.  Crystal structure of the anthrax toxin protective antigen , 1997, Nature.

[29]  A. Shafferman,et al.  Attenuated Nontoxinogenic and Nonencapsulated Recombinant Bacillus anthracis Spore Vaccines Protect against Anthrax , 2000, Infection and Immunity.

[30]  L. Baillie,et al.  Protective efficacy of a recombinant protective antigen against Bacillus anthracis challenge and assessment of immunological markers. , 1998, Vaccine.

[31]  A. Bahrami THE TREATMENT OF ANTHRAX , 1932, Canadian Medical Association journal.

[32]  P. Hanna Anthrax pathogenesis and host response. , 1998, Current topics in microbiology and immunology.

[33]  M. Mock,et al.  Germination of Bacillus anthracis spores within alveolar macrophages , 1999, Molecular microbiology.

[34]  A. Hoffmaster,et al.  Sequence and Organization of pXO1, the Large Bacillus anthracis Plasmid Harboring the Anthrax Toxin Genes , 1999, Journal of bacteriology.

[35]  R. Titball,et al.  Recombinant vaccinia viruses protect against Clostridium perfringens alpha-toxin. , 1999, Viral immunology.

[36]  A. Friedlander,et al.  Vaccination against Anthrax with Attenuated Recombinant Strains of Bacillus anthracis That Produce Protective Antigen , 1999, Infection and Immunity.

[37]  R. Titball,et al.  Bacillus anthracis protective antigen, expressed in Salmonella typhimurium SL 3261, affords protection against anthrax spore challenge. , 1994, Vaccine.

[38]  R. Strange,et al.  Studies on a protective antigen produced in vitro from Bacillus anthracis: medium and methods of production. , 1954, British journal of experimental pathology.

[39]  M Hugh-Jones,et al.  Molecular evolution and diversity in Bacillus anthracis as detected by amplified fragment length polymorphism markers , 1997, Journal of bacteriology.

[40]  Cesare Montecucco,et al.  Anthrax lethal factor cleaves MKK3 in macrophages and inhibits the LPS/IFNγ‐induced release of NO and TNFα , 1999 .