title: Attenuated nontoxinogenic and nonencapsulated recombinant Bacillus anthracis spore vaccines protect against anthrax.
abstract: Several highly attenuated spore-forming nontoxinogenic and nonencapsulated Bacillus anthracis vaccines differing in levels of expression of recombinant protective antigen (rPA) were constructed. Biochemical analyses (including electrospray mass spectroscopy and N terminus amino acid sequencing) as well as biological and immunological tests demonstrated that the rPA retains the characteristics of native PA. A single immunization of guinea pigs with 5 x 10(7) spores of one of these recombinant strains, MASC-10, expressing high levels of rPA (>/=100 microgram/ml) from a constitutive heterologous promoter induced high titers of neutralizing anti-PA antibodies. This immune response was long lasting (at least 12 months) and provided protection against a lethal challenge of virulent (Vollum) anthrax spores. The recombinant B. anthracis spore vaccine appears to be more efficacious than the vegetative cell vaccine. Furthermore, while results clearly suggest a direct correlation between the level of expression of PA and the potency of the vaccine, they also suggest that some B. anthracis spore-associated antigen(s) may contribute in a significant manner to protective immunity.
authors.affiliation: Departments of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 74100, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Cohen
authors.forename: I
authors.initials: I
authors.lastname: Mendelson
authors.forename: Z
authors.initials: Z
authors.lastname: Altboum
authors.forename: D
authors.initials: D
authors.lastname: Kobiler
authors.forename: E
authors.initials: E
authors.lastname: Elhanany
authors.forename: T
authors.initials: T
authors.lastname: Bino
authors.forename: M
authors.initials: M
authors.lastname: Leitner
authors.forename: I
authors.initials: I
authors.lastname: Inbar
authors.forename: H
authors.initials: H
authors.lastname: Rosenberg
authors.forename: Y
authors.initials: Y
authors.lastname: Gozes
authors.forename: R
authors.initials: R
authors.lastname: Barak
authors.forename: M
authors.initials: M
authors.lastname: Fisher
authors.forename: C
authors.initials: C
authors.lastname: Kronman
authors.forename: B
authors.initials: B
authors.lastname: Velan
authors.forename: A
authors.initials: A
authors.lastname: Shafferman
mesh_terms: D000818:Animals; D000881:Anthrax / Q000517:prevention & control*; D000942:Antigens, Bacterial; D001408:Bacillus anthracis / Q000276:immunology; D016667:Bacterial Capsules / Q000276:immunology; D001427:Bacterial Toxins / Q000235:genetics / Q000627:therapeutic use*; D001428:Bacterial Vaccines / Q000627:therapeutic use*; D005069:Evaluation Studies as Topic; D005260:Female; D005798:Genes, Bacterial; D006168:Guinea Pigs; D051379:Mice; D008813:Mice, Inbred ICR; D013171:Spores, Bacterial / Q000276:immunology; D013997:Time Factors; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000627:therapeutic use; D014614:Vaccines, Synthetic / Q000627:therapeutic use
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; C030325:anthrax toxin