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Infection and Immunity, November 2004, p. 6313-6317, Vol. 72, No. 11
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.11.6313-6317.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Functional Analysis of Bacillus anthracis Protective Antigen by Using Neutralizing Monoclonal Antibodies{dagger}

Fabien Brossier,1 Martine Lévy,1 Annie Landier,1 Pierre Lafaye,2 and Michèle Mock1*

Unité Toxines et Pathogénie Bactériennes (URA 2172, CNRS),1 Unité de Génétique et Biochimie du Développement, Institut Pasteur, Paris, France2

Received 1 March 2004/ Returned for modification 1 April 2004/ Accepted 24 July 2004

Protective antigen (PA) is central to the action of the lethal and edema toxins produced by Bacillus anthracis. It is the common cell-binding component, mediating the translocation of the enzymatic moieties (lethal factor [LF] and edema factor) into the cytoplasm of the host cell. Monoclonal antibodies (MAbs) against PA, able to neutralize the activities of the toxins in vitro and in vivo, were screened. Two such MAbs, named 7.5 and 48.3, were purified and further characterized. MAb 7.5 binds to domain 4 of PA and prevents the binding of PA to its cell receptor. MAb 48.3 binds to domain 2 and blocks the cleavage of PA into PA63, a step necessary for the subsequent interaction with the enzymatic moieties. The epitope recognized by this antibody is in a region involved in the oligomerization of PA63; thus, MAb 48.3 does not recognize the oligomer form. MAbs 7.5 and 48.3 neutralize the activities of anthrax toxins produced by B. anthracis in mice. Also, there is an additive effect between the two MAbs against PA and a MAb against LF, in protecting mice against a lethal challenge by the Sterne strain. This work contributes to the functional analysis of PA and offers immunotherapeutic perspectives for the treatment of anthrax disease.

* Corresponding author. Mailing address: Unité Toxines et Pathogénie Bactériennes (URA 2172, CNRS), Institut Pasteur, 28 rue du Dr. Roux, 75724 Paris Cedex 15, France. Phone: (33) 1 45 68 83 12. Fax: (33) 1 45 68 89 54. E-mail: mmock{at}pasteur.fr.

{dagger} This work is dedicated to the memory of Martine Lévy.

Editor: J. T. Barbieri

Infection and Immunity, November 2004, p. 6313-6317, Vol. 72, No. 11
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.11.6313-6317.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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