title: Protein- and DNA-based anthrax toxin vaccines confer protection in guinea pigs against inhalational challenge with Bacillus cereus G9241.
abstract: In the past decade, several Bacillus cereus strains have been isolated from otherwise healthy individuals who succumbed to bacterial pneumonia presenting symptoms resembling inhalational anthrax. One strain was indistinguishable from B. cereus G9241, previously cultured from an individual who survived a similar pneumonia-like illness and which was shown to possess a complete set of plasmid-borne anthrax toxin-encoding homologs. The finding that B. cereus G9241 pathogenesis in mice is dependent on pagA1-derived protective antigen (PA) synthesis suggests that an anthrax toxin-based vaccine may be effective against this toxin-encoding B. cereus strain. Dunkin Hartley guinea pigs were immunized with protein- and DNA-based anthrax toxin-based vaccines, immune responses were evaluated and survival rates were calculated after lethal aerosol exposure with B. cereus G9241 spores. Each vaccine induced seroconversion with the protein immunization regimen eliciting significantly higher serum levels of antigen-specific antibodies at the prechallenge time-point compared with the DNA-protein prime-boost immunization schedule. Complete protection against lethal challenge was observed in all groups with a detectable prechallenge serum titer of toxin neutralizing antibodies. For the first time, we demonstrated that the efficacy of fully defined anthrax toxin-based vaccines was protective against lethal B. cereus G9241 aerosol challenge in the guinea pig animal model.
authors.affiliation: Vaccines and Medical Countermeasures, Biological Defense Research Directorate, Navy Medical Research Center, NMRC-Frederick, Fort Detrick, MD, USA.
authors.forename: John
authors.initials: J
authors.lastname: Palmer
authors.forename: Matt
authors.initials: M
authors.lastname: Bell
authors.forename: Christian
authors.initials: C
authors.lastname: Darko
authors.forename: Roy
authors.initials: R
authors.lastname: Barnewall
authors.forename: Andrea
authors.initials: A
authors.lastname: Keane-Myers
mesh_terms: D000818:Animals; D022122:Anthrax Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000097:blood; D057134:Antibodies, Neutralizing / Q000097:blood; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D000992:Antitoxins / Q000097:blood; D001409:Bacillus cereus / Q000276:immunology*; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D016908:Gram-Positive Bacterial Infections / Q000382:microbiology / Q000517:prevention & control*; D006168:Guinea Pigs; D019570:Inhalation Exposure; D008810:Mice, Inbred C57BL; D018410:Pneumonia, Bacterial / Q000382:microbiology / Q000517:prevention & control*; D016019:Survival Analysis; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
chemical_list: D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing; D000942:Antigens, Bacterial; D000992:Antitoxins; D001427:Bacterial Toxins; D019444:Vaccines, DNA; D022223:Vaccines, Subunit; C030325:anthrax toxin
keywords: DNA vaccine; immunization; inhalation anthrax; recombinant protein vaccine