Attenuated nontoxinogenic and nonencapsulated recombinant Bacillus anthracis spore vaccines protect against anthrax.
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.
Cohen
S
S
Departments of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 74100, Israel.
Mendelson
I
I
Altboum
Z
Z
Kobiler
D
D
Elhanany
E
E
Bino
T
T
Leitner
M
M
Inbar
I
I
Rosenberg
H
H
Gozes
Y
Y
Barak
R
R
Fisher
M
M
Kronman
C
C
Velan
B
B
Shafferman
A
A
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
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; C030325:anthrax toxin