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.
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Cohen S, Mendelson I, Altboum Z, Kobiler D, Elhanany E, Bino T, Leitner M, Inbar I, Rosenberg H, Gozes Y, Barak R, Fisher M, Kronman C, Velan B, Shafferman A (2000) Attenuated nontoxinogenic and nonencapsulated recombinant Bacillus anthracis spore vaccines protect against anthrax Infect Immun68: 4549-58
Cohen S, Mendelson I, Altboum Z, Kobiler D, Elhanany E, Bino T, Leitner M, Inbar I, Rosenberg H, Gozes Y, Barak R, Fisher M, Kronman C, Velan B, Shafferman A (2000) Infect Immun68: 4549-58
