Attenuated Nontoxinogenic and Nonencapsulated Recombinant <i>Bacillus anthracis</i> Spore Vaccines Protect against Anthrax

  • S. Cohen
    <!--label omitted: 1-->Departments of Biochemistry and Molecular Genetics,1
  • I. Mendelson
    <!--label omitted: 1-->Departments of Biochemistry and Molecular Genetics,1
  • Z. Altboum
    <!--label omitted: 2-->Infectious Diseases,2 and
  • D. Kobiler
    <!--label omitted: 2-->Infectious Diseases,2 and
  • E. Elhanany
    <!--label omitted: 1-->Departments of Biochemistry and Molecular Genetics,1
  • T. Bino
    <!--label omitted: 1-->Departments of Biochemistry and Molecular Genetics,1
  • M. Leitner
    <!--label omitted: 1-->Departments of Biochemistry and Molecular Genetics,1
  • I. Inbar
    <!--label omitted: 1-->Departments of Biochemistry and Molecular Genetics,1
  • H. Rosenberg
    <!--label omitted: 1-->Departments of Biochemistry and Molecular Genetics,1
  • Y. Gozes
    <!--label omitted: 2-->Infectious Diseases,2 and
  • R. Barak
    <!--label omitted: 3-->Analytical Chemistry,3 Israel Institute for Biological Research, Ness-Ziona 74100, Israel
  • M. Fisher
    <!--label omitted: 2-->Infectious Diseases,2 and
  • C. Kronman
    <!--label omitted: 1-->Departments of Biochemistry and Molecular Genetics,1
  • B. Velan
    <!--label omitted: 1-->Departments of Biochemistry and Molecular Genetics,1
  • A. Shafferman
    <!--label omitted: 1-->Departments of Biochemistry and Molecular Genetics,1

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<jats:title>ABSTRACT</jats:title> <jats:p> Several highly attenuated spore-forming nontoxinogenic and nonencapsulated <jats:italic>Bacillus anthracis</jats:italic> 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 × 10 <jats:sup>7</jats:sup> 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 <jats:italic>B. anthracis</jats:italic> 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 <jats:italic>B. anthracis</jats:italic> spore-associated antigen(s) may contribute in a significant manner to protective immunity. </jats:p>

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