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Infection and Immunity, August 2000, p. 4549-4558, Vol. 68, No. 8
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Attenuated Nontoxinogenic and Nonencapsulated Recombinant Bacillus anthracis Spore Vaccines Protect against Anthrax

S. Cohen,1,* I. Mendelson,1 Z. Altboum,2 D. Kobiler,2 E. Elhanany,1 T. Bino,1 M. Leitner,1 I. Inbar,1 H. Rosenberg,1 Y. Gozes,2 R. Barak,3 M. Fisher,2 C. Kronman,1 B. Velan,1 and A. Shafferman1

Departments of Biochemistry and Molecular Genetics,1 Infectious Diseases,2 and Analytical Chemistry,3 Israel Institute for Biological Research, Ness-Ziona 74100, Israel

Received 20 March 2000/Returned for modification 1 May 2000/Accepted 19 May 2000

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 × 107 spores of one of these recombinant strains, MASC-10, expressing high levels of rPA (>= 100 µg/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.

* Corresponding author. Mailing address: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, P.O. Box 19, Ness-Ziona 74100, Israel. Phone: 972-8-9381718. Fax: 972-8-9401404. E-mail: avigdor{at}iibr.gov.il.

Infection and Immunity, August 2000, p. 4549-4558, Vol. 68, No. 8
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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